Arthur Weiss, MD, PhD

Professor

Research Interest:

The response of lymphocytes to antigen which initiates an antigen specific immune response also represents a unique opportunity to study how complex molecular interactions between cells can lead to developmental decisions, cell differentiation and proliferation. We are interested in understanding how receptors involved in antigen recognition can initiate signal transduction events that regulate cell responses in the immune system. We know that receptors involved in antigen recognition functionally interact with tyrosine kinases and phosphatases, enzymes that regulate protein phosphorylation, to induce signaling pathways that regulate cellular responses and gene expression. We are using genetically selective small molecule inhibitors of kinases together with phosphatase mutants to study how thresholds for the initiation of immune responses are set and how feedback circuits influence responses. We would like to understand how the tyrosine kinases and phosphatases in these pathways are regulated and how they control cellular responses in development, in normal immune responses and in autoimmune diseases such as lupus and rheumatoid arthritis.
Education
Residency, - Rheumatology, University of California, San Francisco
Honors and Awards
  • Eberly Lecture, U. Pittsburgh, 2019
  • Establishment of Arthur Weiss Lectureship in Rheumatology and Immunology, UCSF, 2019
  • Associate Member, European Molecular Biology Organization, 2017
  • Ephraim P. Engleman Memorial Lecture, American College of Rheumatology, 2016
  • Merit Award, NIH, NIAID, 2016
  • Frank and Shirley Fitch Lecture, University of Chicago, 2016
  • Lifetime Achievement Award, American Association of Immunologists, 2012
  • Lifetime Achievement in Mentoring Award, UCSF, 2012
  • Distinguished Investigator Award, American College of Rheumatology, 2004
  • Member, Institute of Medicine, 2004
  • Member, National Academy of Sciences, 2004
  • Fellow, American Academy of Arts and Sciences, 2003
  • American Association of Immunologists-Huang Foundation Meritorious Career Award, American Association of Immunologists, 2001
  • Forty-first Faculty Research Lecturer, UCSF, 1998
  • Lee C. Howley Prize, Arthritis Foundation, 1997
  • Junior Investigator Award, American Association of Immunologists, 1993
  • Henry Kunkel Young Investigator Award, American College of Rheumatology, 1990
  • Young Investigator Award, Western Society for Clinical Investigation, 1990
Websites
Publications
  1. Bruton's Tyrosine Kinase Membrane Dynamics and Signaling.
  2. How the T Cell Signaling Network Processes Information to Discriminate between Self and Cognate Ligands.
  3. CD45 functions as a signaling gatekeeper in T cells.
  4. Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.
  5. Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis.
  6. CRACR2a is a calcium-activated dynein adaptor protein that regulates endocytic traffic.
  7. The Gp1ba-Cre transgenic mouse: a new model to delineate platelet and leukocyte functions.
  8. Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT.
  9. Fine-tuning of substrate preferences of the Src-family kinase Lck revealed through a high-throughput specificity screen.
  10. Maintenance of murine platelet homeostasis by the kinase Csk and phosphatase CD148.
  11. IL-2Rß abundance differentially tunes IL-2 signaling dynamics in CD4+ and CD8+ T cells.
  12. TCR Signaling: Mechanisms of Initiation and Propagation.
  13. A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45.
  14. Destabilizing the autoinhibitory conformation of Zap70 induces up-regulation of inhibitory receptors and T cell unresponsiveness.
  15. IL-2 Modulates the TCR Signaling Threshold for CD8 but Not CD4 T Cell Proliferation on a Single-Cell Level.
  16. Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen.
  17. Endogenous Nur77 Is a Specific Indicator of Antigen Receptor Signaling in Human T and B Cells.
  18. Positive Regulation of Lyn Kinase by CD148 Is Required for B Cell Receptor Signaling in B1 but Not B2 B Cells.
  19. An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor.
  20. Human LAT mutation results in immune deficiency and autoimmunity but also raises questions about signaling pathways.
  21. CD28 Costimulation: From Mechanism to Therapy.
  22. Essential biphasic role for JAK3 catalytic activity in IL-2 receptor signaling.
  23. A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70.
  24. Targeted Activation of B Cell Autoimmunity Checkpoints in Acute Lymphoblastic Leukemia.
  25. An extracatalytic function of CD45 in B cells is mediated by CD22.
  26. LynA regulates an inflammation-sensitive signaling checkpoint in macrophages.
  27. Small molecule inhibition of Csk alters affinity recognition by T cells.
  28. The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway.
  29. Commentary: "The Role of T3 Surface Molecules in the Activation of Human Cells: A Two-Stimulus Requirement for IL-2 Production Reflects Events Occurring at a Pretranslational Level".
  30. Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia.
  31. Combinatorial proteomic analysis of intercellular signaling applied to the CD28 T-cell costimulatory receptor.
  32. Unbiased modifier screen reveals that signal strength determines the regulatory role murine TLR9 plays in autoantibody production.
  33. Erratum: Quantitative and temporal requirements revealed for Zap70 catalytic activity during T cell development.
  34. Combined immunodeficiency due to MALT1 mutations, treated by hematopoietic cell transplantation.
  35. Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding.
  36. Insights into the initiation of TCR signaling.
  37. A sharp T-cell antigen receptor signaling threshold for T-cell proliferation.
  38. Zap70 is essential for long-term survival of naive CD8 T cells.
  39. Distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and T-cell receptor signaling patterns.
  40. Quantitative and temporal requirements revealed for Zap70 catalytic activity during T cell development.
  41. Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation.
  42. Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210.
  43. Distinct structural and catalytic roles for Zap70 in formation of the immunological synapse in CTL.
  44. Protein kinase Cd promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance.
  45. Investigation of Novel Zap-70 Functionality in T Cell Signaling Pathways using Computational Modeling.
  46. Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling.
  47. Tony Pawson: Modular protein domains and the links to intracellular signaling.
  48. Novel tools to dissect the dynamic regulation of TCR signaling by the kinase Csk and the phosphatase CD45.
  49. Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4? T cells.
  50. DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape.
  51. The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases.
  52. Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker.
  53. The structural wedge domain of the receptor-like tyrosine phosphatase CD45 enforces B cell tolerance by regulating substrate specificity.
  54. Monovalent and multivalent ligation of the B cell receptor exhibit differential dependence upon Syk and Src family kinases.
  55. Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function.
  56. Endogenous antigen tunes the responsiveness of naive B cells but not T cells.
  57. Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells.
  58. A resource for the conditional ablation of microRNAs in the mouse.
  59. The membrane environment can promote or suppress bistability in cell signaling networks.
  60. Lymphocyte signaling: a Tuscan affair.
  61. Quantitative differences in CD45 expression unmask functions for CD45 in B-cell development, tolerance, and survival.
  62. Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease.
  63. Receptor-like tyrosine phosphatases CD45 and CD148 have distinct functions in chemoattractant-mediated neutrophil migration and response to S. aureus.
  64. Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRa gene expression.
  65. SCIMP, a transmembrane adaptor protein involved in major histocompatibility complex class II signaling.
  66. Feedback circuits monitor and adjust basal Lck-dependent events in T cell receptor signaling.
  67. Ca-dependent Ras/Erk signaling mediates negative selection of autoreactive B cells.
  68. Regulation of Src family kinases involved in T cell receptor signaling by protein-tyrosine phosphatase CD148.
  69. Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.
  70. STIM1, PKC-d and RasGRP set a threshold for proapoptotic Erk signaling during B cell development.
  71. Differential requirements for CD45 in NK-cell function reveal distinct roles for Syk-family kinases.
  72. The Src-like adaptor protein regulates GM-CSFR signaling and monocytic dendritic cell maturation.
  73. A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity.
  74. Proline-rich tyrosine kinase-2 is critical for CD8 T-cell short-lived effector fate.
  75. Regulation of thymocyte positive selection and motility by GIT2.
  76. ZAP-70: an essential kinase in T-cell signaling.
  77. CD45-Csk phosphatase-kinase titration uncouples basal and inducible T cell receptor signaling during thymic development.
  78. The right team at the right time to go for a home run: tyrosine kinase activation by the TCR.
  79. Chapter 95 CD45.
  80. Stability of an autoinhibitory interface in the structure of the tyrosine kinase ZAP-70 impacts T cell receptor response.
  81. SLAP, a regulator of immunoreceptor ubiquitination, signaling, and trafficking.
  82. A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune disease versus autoimmune reactivity.
  83. TCR signal transduction: opening the black box.
  84. Molecular origin and functional consequences of digital signaling and hysteresis during Ras activation in lymphocytes.
  85. PTPN22 deficiency cooperates with the CD45 E613R allele to break tolerance on a non-autoimmune background.
  86. The structure, regulation, and function of ZAP-70.
  87. The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis.
  88. Antigen receptor signaling in the rheumatic diseases.
  89. Digital signaling and hysteresis characterize ras activation in lymphoid cells.
  90. Differential impact of the CD45 juxtamembrane wedge on central and peripheral T cell receptor responses.
  91. Alternative splicing of CD45: the tip of the iceberg.
  92. Origin of the sharp boundary that discriminates positive and negative selection of thymocytes.
  93. Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice.
  94. B cells drive lymphocyte activation and expansion in mice with the CD45 wedge mutation and Fas deficiency.
  95. The proline-rich sequence of CD3epsilon controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes.
  96. Inhibition of ZAP-70 kinase activity via an analog-sensitive allele blocks T cell receptor and CD28 superagonist signaling.
  97. Structurally distinct phosphatases CD45 and CD148 both regulate B cell and macrophage immunoreceptor signaling.
  98. Opposing functions of the T cell receptor kinase ZAP-70 in immunity and tolerance differentially titrate in response to nucleotide substitutions.
  99. Distinct roles for Syk and ZAP-70 during early thymocyte development.
  100. Differential expression of the ARF GAP genes GIT1 and GIT2 in mouse tissues.
  101. Structural basis for the inhibition of tyrosine kinase activity of ZAP-70.
  102. Coupling Ca2+ store release to Icrac channel activation in B lymphocytes requires the activity of Lyn and Syk kinases.
  103. Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes.
  104. The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated virulence.
  105. Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner.
  106. The Phenotypic Consequences of an Activating Mutation in the Juxtamembrane Wedge of CD45 Is Sensitive to Genetic Modifiers.
  107. ZAP-70 Enhances IgM Signaling in Chronic Lymphocytic Leukemia Cells Independent of Its Tyrosine Kinase Activity.
  108. Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4.
  109. Dysregulation of signaling pathways in CD45-deficient NK cells leads to differentially regulated cytotoxicity and cytokine production.
  110. Small molecule inhibition of ZAP-70 kinase activity.
  111. SRC-like adaptor protein regulates B cell development and function.
  112. Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex.
  113. The juxtamembrane wedge negatively regulates CD45 function in B cells.
  114. Discovering the TCR beta-chain by subtraction.
  115. Src-like adaptor protein down-regulates T cell receptor (TCR)-CD3 expression by targeting TCRzeta for degradation.
  116. A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells.
  117. Intramolecular regulatory switch in ZAP-70: analogy with receptor tyrosine kinases.
  118. Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1.
  119. Twisting tails exposed: the evidence for TCR conformational change.
  120. Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation.
  121. SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase.
  122. Regulated expression of the receptor-like tyrosine phosphatase CD148 on hemopoietic cells.
  123. Lymphocyte activation.
  124. A proline-rich motif in the C terminus of Akt contributes to its localization in the immunological synapse.
  125. T cell receptor engagement leads to phosphorylation of clathrin heavy chain during receptor internalization.
  126. Jurkat T cells and development of the T-cell receptor signalling paradigm.
  127. Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation.
  128. Expression and function of Tec, Itk, and Btk in lymphocytes: evidence for a unique role for Tec.
  129. T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression.
  130. The tyrosine phosphatase CD148 is excluded from the immunologic synapse and down-regulates prolonged T cell signaling.
  131. Linker for activation of T cells, zeta-associated protein-70, and Src homology 2 domain-containing leukocyte protein-76 are required for TCR-induced microtubule-organizing center polarization.
  132. The PI-3 kinase/Akt pathway and T cell activation: pleiotropic pathways downstream of PIP3.
  133. Synergistic assembly of linker for activation of T cells signaling protein complexes in T cell plasma membrane domains.
  134. Chapter 114 CD45.
  135. Dynamics of p56lck translocation to the T cell immunological synapse following agonist and antagonist stimulation.
  136. Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription.
  137. It's all Rel-ative: NF-kappaB and CD28 costimulation of T-cell activation.
  138. Negative regulation of CD45 by differential homodimerization of the alternatively spliced isoforms.
  139. The inducible expression of the tumor suppressor gene PTEN promotes apoptosis and decreases cell size by inhibiting the PI3K/Akt pathway in Jurkat T cells.
  140. Reciprocal regulation of lymphocyte activation by tyrosine kinases and phosphatases.
  141. CD45: a critical regulator of signaling thresholds in immune cells.
  142. PTPRC (CD45) is not associated with the development of multiple sclerosis in U.S. patients.
  143. The Src-like adaptor protein downregulates the T cell receptor on CD4+CD8+ thymocytes and regulates positive selection.
  144. Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes.
  145. Regulatory mechanisms for receptor protein tyrosine phosphatases.
  146. Endogenous CD28 expressed on myeloma cells up-regulates interleukin-8 production: implications for multiple myeloma progression.
  147. Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT.
  148. Identification of the minimal tyrosine residues required for linker for activation of T cell function.
  149. A CD45 polymorphism associated with multiple sclerosis disrupts an exonic splicing silencer.
  150. Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation.
  151. A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT.
  152. Characterization of promoter region and genomic structure of the murine and human genes encoding Src like adapter protein.
  153. Akt provides the CD28 costimulatory signal for up-regulation of IL-2 and IFN-gamma but not TH2 cytokines.
  154. Distinct T cell developmental consequences in humans and mice expressing identical mutations in the DLAARN motif of ZAP-70.
  155. Mechanisms of signaling by the hematopoietic-specific adaptor proteins, SLP-76 and LAT and their B cell counterpart, BLNK/SLP-65.
  156. T cell receptor signalling.
  157. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity.
  158. Lymphocytes with a complex: adapter proteins in antigen receptor signaling.
  159. Signal transduction by the TCR for antigen.
  160. HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1.
  161. Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling.
  162. A guanine nucleotide exchange factor-independent function of Vav1 in transcriptional activation.
  163. Tetracycline-controllable selection of CD4(+) T cells: half-life and survival signals in the absence of major histocompatibility complex class II molecules.
  164. A model system for activation-induced alternative splicing of CD45 pre-mRNA in T cells implicates protein kinase C and Ras.
  165. Localization of LAT in glycolipid-enriched microdomains is required for T cell activation.
  166. Pre-T cell receptor signals are responsible for the down-regulation of Syk protein tyrosine kinase expression.
  167. Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus.
  168. Interdomain B in ZAP-70 regulates but is not required for ZAP-70 signaling function in lymphocytes.
  169. The adapter proteins LAT and SLP-76 are required for T-cell activation.
  170. Nuclear factor of activated T cells and AP-1 are insufficient for IL-2 promoter activation: requirement for CD28 up-regulation of RE/AP.
  171. Differential requirements for ZAP-70 in TCR signaling and T cell development.
  172. LAT is required for TCR-mediated activation of PLCgamma1 and the Ras pathway.
  173. A Nck-Pak1 signaling module is required for T-cell receptor-mediated activation of NFAT, but not of JNK.
  174. Switching signals on or off by receptor dimerization.
  175. Uncoupling of nonreceptor tyrosine kinases from PLC-gamma1 in an SLP-76-deficient T cell.
  176. Anti-peptide antibodies detect conformational changes of the inter-SH2 domain of ZAP-70 due to binding to the zeta chain and to intramolecular interactions.
  177. Regulation of TCR signal transduction in murine thymocytes by multiple TCR zeta-chain signaling motifs.
  178. Itk and Fyn make independent contributions to T cell activation.
  179. Itk negatively regulates induction of T cell proliferation by CD28 costimulation.
  180. CD28 mediates transcriptional upregulation of the interleukin-2 (IL-2) promoter through a composite element containing the CD28RE and NF-IL-2B AP-1 sites.
  181. ZAP-70 protein tyrosine kinase is constitutively targeted to the T cell cortex independently of its SH2 domains.
  182. The Vav binding site (Y315) in ZAP-70 is critical for antigen receptor-mediated signal transduction.
  183. Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling.
  184. T cell antigen receptor signal transduction.
  185. The Syk protein tyrosine kinase can function independently of CD45 or Lck in T cell antigen receptor signaling.
  186. Reconstitution of T cell receptor signaling in ZAP-70-deficient cells by retroviral transduction of the ZAP-70 gene.
  187. alpha beta T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases.
  188. c-rel regulation of IL-2 gene expression may be mediated through activation of AP-1.
  189. Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C.
  190. Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation.
  191. SH2 domain function is essential for the role of the Lck tyrosine kinase in T cell receptor signal transduction.
  192. Lck regulates the tyrosine phosphorylation of the T cell receptor subunits and ZAP-70 in murine thymocytes.
  193. Dominant-negative zeta-associated protein 70 inhibits T cell antigen receptor signaling.
  194. CD28-mediated costimulation in the absence of phosphatidylinositol 3-kinase association and activation.
  195. Absence of ZAP-70 prevents signaling through the antigen receptor on peripheral blood T cells but not on thymocytes.
  196. Molecular and genetic insights into T-cell antigen receptor signaling.
  197. Molecular and genetic insights into the role of protein tyrosine kinases in T cell receptor signaling.
  198. A functional T-cell receptor signaling pathway is required for p95vav activity.
  199. Multiple kinases mediate T-cell-receptor signaling.
  200. The protein tyrosine kinase ZAP-70 can associate with the SH2 domain of proto-Vav.
  201. ZAP-70 is constitutively associated with tyrosine-phosphorylated TCR zeta in murine thymocytes and lymph node T cells.
  202. The role of protein kinase C in the regulation of extracellular signal-regulated kinase by the T cell antigen receptor.
  203. The catalytic activity of the CD45 membrane-proximal phosphatase domain is required for TCR signaling and regulation.
  204. GRB2 and phospholipase C-gamma 1 associate with a 36- to 38-kilodalton phosphotyrosine protein after T-cell receptor stimulation.
  205. Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase.
  206. ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency.
  207. Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling.
  208. The cytoplasmic domain of CD28 is both necessary and sufficient for costimulation of interleukin-2 secretion and association with phosphatidylinositol 3'-kinase.
  209. Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex.
  210. Production and characterization of monoclonal antibodies specific for the murine T cell receptor zeta chain.
  211. Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases.
  212. Signal transduction by lymphocyte antigen receptors.
  213. Molecular and genetic insights into T cell antigen receptor signal transduction.
  214. The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction.
  215. Signal transduction events leading to T-cell lymphokine gene expression.
  216. Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase.
  217. T cell antigen receptor signal transduction: a tale of tails and cytoplasmic protein-tyrosine kinases.
  218. Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain.
  219. CD45 specifically modulates binding of Lck to a phosphopeptide encompassing the negative regulatory tyrosine of Lck.
  220. Molecular Dissection of T-Cell Antigen Receptor Signal Transduction.
  221. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain.
  222. The protein tyrosine kinase inhibitor herbimycin A, but not genistein, specifically inhibits signal transduction by the T cell antigen receptor.
  223. Regulation of T-cell lymphokine gene transcription by the accessory molecule CD28.
  224. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor.
  225. Restoration of T cell receptor-mediated signal transduction by transfection of CD45 cDNA into a CD45-deficient variant of the Jurkat T cell line.
  226. New insights into T-cell antigen receptor structure and signal transduction.
  227. CD28 and T cell antigen receptor signal transduction coordinately regulate interleukin 2 gene expression in response to superantigen stimulation.
  228. Tyrosine phosphorylation of vav proto-oncogene product containing SH2 domain and transcription factor motifs.
  229. Regulation of protein tyrosine kinase activation by the T-cell antigen receptor zeta chain.
  230. The zeta chain is associated with a tyrosine kinase and upon T-cell antigen receptor stimulation associates with ZAP-70, a 70-kDa tyrosine phosphoprotein.
  231. Signal transduction by the T cell antigen receptor.
  232. Functional activation of the T-cell antigen receptor induces tyrosine phosphorylation of phospholipase C-gamma 1.
  233. Regions of the T cell receptor alpha and beta chains that are responsible for interactions with CD3.
  234. Signaling via the inositol phospholipid pathway by T cell antigen receptor is limited by receptor number.
  235. Tyrosine phosphatase CD45 is required for T-cell antigen receptor and CD2-mediated activation of a protein tyrosine kinase and interleukin 2 production.
  236. The regulation of T-cell antigen receptor signal transduction function.
  237. Regulation of interleukin-2 gene enhancer activity by the T cell accessory molecule CD28.
  238. Molecular and genetic insights into T cell antigen receptor structure and function.
  239. Stimulation of the phosphatidylinositol pathway can induce T-cell activation.
  240. Structure and function of the T cell antigen receptor.
  241. Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway.
  242. T-lymphocyte-antigen interactions in transplant rejection.
  243. A transfected human muscarinic receptor fails to substitute for the T cell antigen receptor complex in CD2-initiated signal transduction.
  244. Function of a heterologous muscarinic receptor in T cell antigen receptor signal transduction mutants.
  245. Heterogeneity of protein kinase C isoenzyme gene expression in human T cell lines. Protein kinase C-beta is not required for several T cell functions.
  246. Ligand-induced association between the T-cell antigen receptor and two glycoproteins.
  247. Use of Somatic Cell Mutants to Study the Signal Transduction Function of the T Cell Antigen Receptor.
  248. Use of somatic cell mutants to study the signal transduction function of the T cell antigen receptor.
  249. The lysine residue in the membrane-spanning domain of the beta chain is necessary for cell surface expression of the T cell antigen receptor.
  250. At least two non-antigen-binding molecules are required for signal transduction by the T-cell antigen receptor.
  251. The CD2 ligand LFA-3 activates T cells but depends on the expression and function of the antigen receptor.
  252. New clues about T-cell antigen receptor complex function.
  253. Early signal transduction by the antigen receptor without commitment to T cell activation.
  254. CHAPTER 4 REGULATION OF INTERLEUKIN 2 PRODUCTION BY THE T CELL ANTIGEN RECEPTOR.
  255. Function of the antigen receptor in T cell activation.
  256. Generation and analysis of a T-lymphocyte somatic mutant for studying molecular aspects of signal transduction by the antigen receptor.
  257. Role of the T3/T-Cell Antigen Receptor Complex in T-Cell Activation.
  258. The initiation of human T lymphocyte activation.
  259. Identification and sequence of a fourth human T cell antigen receptor chain.
  260. The activation of T lymphocytes.
  261. Functional competency of T cell antigen receptors in human thymus.
  262. Evidence that the T cell antigen receptor may not be involved in cytotoxicity mediated by gamma/delta and alpha/beta thymic cell lines.
  263. The T-cell antigen receptor regulates sustained increases in cytoplasmic free Ca2+ through extracellular Ca2+ influx and ongoing intracellular Ca2+ mobilization.
  264. The gamma T-cell antigen receptor.
  265. The role of protein kinase C in transmembrane signaling by the T cell antigen receptor complex. Effects of stimulation with soluble or immobilized CD3 antibodies.
  266. Isolation and characterization of a T-lymphocyte somatic mutant with altered signal transduction by the antigen receptor.
  267. Molecular diversity of the human T-gamma constant region genes.
  268. Cell surface T3 expression requires the presence of both alpha- and beta-chains of the T cell receptor.
  269. Requirements for triggering of lysis by cytolytic T lymphocyte clones.
  270. Ligand-receptor interactions required for commitment to the activation of the interleukin 2 gene.
  271. The T cell antigen receptor complex expressed on normal peripheral blood CD4-, CD8- T lymphocytes. A CD3-associated disulfide-linked gamma chain heterodimer.
  272. Thy-1-mediated T-cell activation requires co-expression of CD3/Ti complex.
  273. Characterization of an expressed CD3-associated Ti gamma-chain reveals C gamma domain polymorphism.
  274. A 275 basepair fragment at the 5' end of the interleukin 2 gene enhances expression from a heterologous promoter in response to signals from the T cell antigen receptor.
  275. Cell surface molecules and early events involved in human T lymphocyte activation.
  276. Specific antigen-Ia activation of transfected human T cells expressing murine Ti alpha beta-human T3 receptor complexes.
  277. The role of the antigen receptor/T3 complex in T-cell activation.
  278. Presence of Ti (WT31) negative T lymphocytes in normal blood and thymus.
  279. Distinct epitopes on the T cell antigen receptor of HPB-ALL tumor cells identified by monoclonal antibodies.
  280. Synergy between the T3/antigen receptor complex and Tp44 in the activation of human T cells.
  281. Differential effect of cyclosporin A on activation signaling in human T cell lines.
  282. A transferrin receptor antibody represents one signal for the induction of IL 2 production by a human T cell line.
  283. The role of the T3/antigen receptor complex in T-cell activation.
  284. T cell activation: differences in the signals required for IL 2 production by nonactivated and activated T cells.
  285. Transmembrane signalling by the T3-antigen receptor complex.
  286. Reconstitution of an active surface T3/T-cell antigen receptor by DNA transfer.
  287. Activation of a human T cell line: a two-stimulus requirement in the pretranslational events involved in the coordinate expression of interleukin 2 and gamma-interferon genes.
  288. The antigen receptor on a human T cell line initiates activation by increasing cytoplasmic free calcium.
  289. Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line.
  290. Role of T3 surface molecules in human T-cell activation: T3-dependent activation results in an increase in cytoplasmic free calcium.
  291. The role of T3 surface molecules in the activation of human T cells: a two-stimulus requirement for IL 2 production reflects events occurring at a pre-translational level.
  292. The role of T3 in the activation of human T cells.
  293. Inhibition of cytolytic T lymphocyte clones reactive with Moloney leukemia virus-associated antigens by monoclonal antibodies: a direct approach to the study of H-2 restriction.
  294. Antigenic specificity of the cytolytic T lymphocyte response to murine sarcoma virus-induced tumors. III. Characterization of cytolytic T lymphocyte clones specific for Moloney leukemia virus-associated cell surface antigens.
  295. Suppression of rat renal allograft rejection by antigen and antibody.
  296. Selective suppression of humoral and cell-mediated immune responses to rat alloantigens by monoclonal antibodies produced by hybridoma cell lines.
  297. Immune reactivity of cells from long-term rat renal allograft survivors.
  298. Immunological memory is regulated in the enhanced rat renal allograft recipient.
  299. Graft enhancement and antiidiotypic antibody. Lymphocytes from long-term rat renal allograft recipients have normal responsiveness in vitro.
  300. Suppression of the plaque-forming cell response by macrophages present in the normal rat spleen.
  301. Absence of immunologic memory in recipients of enhanced renal allografts.
  302. Selective suppression of reactivity to rat histocompatibility antigens by hybridoma antibodies.
  303. Macrophages suppress CTL generation in rat mixed leukocyte cultures.
  304. Suppression of adult rat lymphoid proliferative responses by homologous neonatal serum.
  305. Antigen cap formation in cultured fibroblasts: a reflection of membrane fluidity and of cell motility.