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PMID: 7905824 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Genetic and immunochemical evidence for CD4-dependent association of p56lck with the alpha beta T-cell receptor (TCR): regulation of TCR-induced activation.

The EMBO journal ·Vol. 13 ·No. 1 ·1994-01-01 ·Pages 90-9

Díez-Orejas R, Ballester S, Feito MJ, Ojeda G, Criado G, Ronda M, Portolés P, Rojo JM

Abstract

Recent observations suggest that the tyrosine kinase p56lck is involved in the transduction of transmembrane signals through the antigen specific T cell receptor (TCR) in CD4+ T cells. By means of in vitro kinase assays, we have found that p56lck coprecipitated with the TCR from lysates of a murine CD4+ T cell line in the absence of TCR-mediated stimuli. Analysis of CD4- mutants and CD4-transfected cells shows that p56lck-TCR association occurred only when CD4 was present. The functional importance of CD4:p56lck-TCR association was demonstrated by low activating potential of rare clonotypic antibodies which did not coprecipitate CD4:p56lck, as well as by total or partial loss of anti-TCR or antigen induced stimulation in CD4- cells, which could be recovered by CD4 transfection. Complementation assays using different anti-TCR antibodies suggest that cross linking of TCR-p56lck:CD4 plus structural changes in the complex are needed for efficient transduction of activating signals through the TCR in these cells.

MeSH Terms
Animals CD3 Complex/metabolism CD4 Antigens/genetics,metabolism CD4-Positive T-Lymphocytes/immunology,metabolism Cell Line Flow Cytometry Lymphocyte Activation/physiology Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Mice Mice, Inbred C3H Mutation Precipitin Tests Protein-Tyrosine Kinases/metabolism Receptors, Antigen, T-Cell, alpha-beta/metabolism Signal Transduction Transfection
Chemicals
CD3 Complex CD4 Antigens Receptors, Antigen, T-Cell, alpha-beta Protein-Tyrosine Kinases Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Díez-Orejas R
Centro de Investigaciones Biológicas, C.S.I.C., Madrid, Spain.
Ballester S
Feito M J
Ojeda G
Criado G
Ronda M
Portolés P
Rojo J M
References (73)
73 references, click to expand
  1. Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5.
    Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2945-9 PMID: 1372996
  2. Profound block in thymocyte development in mice lacking p56lck.
    Nature. 1992 May 14;357(6374):161-4 PMID: 1579166
  3. Differential regulation of T cell antigen responsiveness by isoforms of the src-related tyrosine protein kinase p59fyn.
    J Exp Med. 1992 Jun 1;175(6):1483-92 PMID: 1375262
  4. The T cell receptor as a multicomponent signalling machine: CD4/CD8 coreceptors and CD45 in T cell activation.
    Annu Rev Immunol. 1992;10:645-74 PMID: 1534242
  5. A tyrosine-phosphorylated 70-kDa protein binds a photoaffinity analogue of ATP and associates with both the zeta chain and CD3 components of the activated T cell antigen receptor.
    J Biol Chem. 1992 Jun 15;267(17):11685-8 PMID: 1534800
  6. Association of tyrosine kinase p56lck with CD4 inhibits the induction of growth through the alpha beta T-cell receptor.
    Nature. 1992 Jul 23;358(6384):328-31 PMID: 1322497
  7. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor.
    Cell. 1992 Aug 21;70(4):585-93 PMID: 1505025
  8. Biochemical evidence of the physical association of the majority of CD3 delta chains with the accessory/co-receptor molecules CD4 and CD8 on nonactivated T lymphocytes.
    Eur J Immunol. 1992 Oct;22(10):2475-9 PMID: 1396954
  9. Selective association between MHC class I-restricted T cell receptors, CDS, and activated tyrosine kinases on thymocytes undergoing positive selection.
    J Immunol. 1992 Nov 15;149(10):3142-9 PMID: 1431093
  10. Specific affinity fractionation of lymphocytes using glass or plastic bead columns.
    Scand J Immunol. 1976 Jun;Suppl 5:23-30 PMID: 1052388
  11. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody.
    Eur J Immunol. 1979 Apr;9(4):301-6 PMID: 89034
  12. Functional activities of antibodies against brain-associated T cell antigens. I. Induction of T cell proliferation.
    Eur J Immunol. 1981 Jul;11(7):584-92 PMID: 6974646
  13. Antigens involved in mouse cytolytic T-lymphocyte (CTL)-mediated killing: functional screening and topographic relationship.
    Cell Immunol. 1982 Oct;73(1):1-11 PMID: 6983917
  14. Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development.
    Immunol Rev. 1982;69:5-23 PMID: 6984001
  15. Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells.
    J Exp Med. 1983 Sep 1;158(3):836-56 PMID: 6193236
  16. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  17. T cell subsets and the recognition of MHC class.
    Immunol Rev. 1983;74:129-42 PMID: 6226585
  18. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity.
    Immunol Rev. 1983;74:29-56 PMID: 6195085
  19. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.
    J Immunol Methods. 1983 Dec 16;65(1-2):55-63 PMID: 6606682
  20. Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2.
    J Immunol. 1984 Sep;133(3):1339-45 PMID: 6235287
  21. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor.
    J Immunol. 1985 Jun;134(6):3994-4000 PMID: 2580901
  22. A method to detect and characterize point mutations in transcribed genes: amplification and overexpression of the mutant c-Ki-ras allele in human tumor cells.
    Proc Natl Acad Sci U S A. 1985 Nov;82(22):7575-9 PMID: 2415964
  23. Direct interactions between B and T lymphocytes bearing complementary receptors.
    J Exp Med. 1986 Jan 1;163(1):189-202 PMID: 3484511
  24. The role of the T3/antigen receptor complex in T-cell activation.
    Annu Rev Immunol. 1986;4:593-619 PMID: 2939858
  25. Antigen activation of murine T cells induces tyrosine phosphorylation of a polypeptide associated with the T cell antigen receptor.
    Cell. 1986 Sep 26;46(7):1083-90 PMID: 2428504
  26. Cross-linking of the T cell receptor complex with the subset-specific differentiation antigen stimulates interleukin 2 receptor expression in human CD4 and CD8 T cells.
    Eur J Immunol. 1987 Apr;17(4):529-34 PMID: 3106067
  27. Effective activation of resting mouse T lymphocytes by cross-linking submitogenic concentrations of the T cell antigen receptor with either Lyt-2 or L3T4.
    Eur J Immunol. 1987 May;17(5):643-50 PMID: 3108015
  28. Evidence for a physical association of CD4 and the CD3:alpha:beta T-cell receptor.
    Nature. 1987 Jul 16-22;328(6127):260-3 PMID: 3110627
  29. Interaction between CD4 and class II MHC molecules mediates cell adhesion.
    Nature. 1987 Nov 19-25;330(6145):256-9 PMID: 2823150
  30. The biologic activity of anti-T cell receptor V region monoclonal antibodies is determined by the epitope recognized.
    J Immunol. 1988 Feb 15;140(4):1081-8 PMID: 2449495
  31. Comodulation of CD3 and CD4. Evidence for a specific association between CD4 and approximately 5% of the CD3:T cell receptor complexes on helper T lymphocytes.
    J Immunol. 1988 Mar 15;140(6):1732-7 PMID: 2964480
  32. Identification of an immunodominant region on the I-A beta chain using site-directed mutagenesis and DNA-mediated gene transfer.
    J Exp Med. 1988 Feb 1;167(2):473-87 PMID: 2450160
  33. CD4+ T cells: specificity and function.
    Immunol Rev. 1988 Jan;101:39-80 PMID: 2450827
  34. The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes.
    Proc Natl Acad Sci U S A. 1988 Jul;85(14):5190-4 PMID: 2455897
  35. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck.
    Cell. 1988 Oct 21;55(2):301-8 PMID: 3262426
  36. Cell-cell adhesion mediated by CD8 and MHC class I molecules.
    Nature. 1988 Nov 3;336(6194):79-81 PMID: 3263576
  37. Molecular dynamics in the membranes of helper T cells.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):8216-20 PMID: 2973062
  38. Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8.
    Nature. 1989 Mar 23;338(6213):345-7 PMID: 2784196
  39. Physical association of CD4 and the T-cell receptor can be induced by anti-T-cell receptor antibodies.
    Proc Natl Acad Sci U S A. 1989 May;86(9):3311-5 PMID: 2470100
  40. Monoclonal antibodies to murine CD3 epsilon define distinct epitopes, one of which may interact with CD4 during T cell activation.
    J Immunol. 1989 Jun 15;142(12):4169-75 PMID: 2470817
  41. The role of L3T4 in T cell activation: L3T4 may be both an Ia-binding protein and a receptor that transduces a negative signal.
    J Mol Cell Immunol. 1986;2(4):179-90 PMID: 3509916
  42. The role of the murine L3T4 molecule in T cell activation: differential effects of anti-L3T4 on activation by monoclonal anti-receptor antibodies.
    J Mol Cell Immunol. 1987;3(2):121-31 PMID: 2978238
  43. Asymmetry in the recognition of antigen: self class II MHC and non-self class II MHC molecules by the same T-cell receptor.
    J Mol Cell Immunol. 1989;4(3):129-37 PMID: 2475125
  44. The co-receptor function of murine CD4.
    Immunol Rev. 1989 Jun;109:77-92 PMID: 2670749
  45. T-cell receptor-CD4 physical association in a murine T-cell hybridoma: induction by antigen receptor ligation.
    Proc Natl Acad Sci U S A. 1989 Nov;86(21):8531-5 PMID: 2530583
  46. Mutations of the platelet-derived growth factor receptor that cause a loss of ligand-induced conformational change, subtle changes in kinase activity, and impaired ability to stimulate DNA synthesis.
    Mol Cell Biol. 1989 Oct;9(10):4473-8 PMID: 2479827
  47. Epidermal growth factor binding induces a conformational change in the external domain of its receptor.
    EMBO J. 1989 Dec 20;8(13):4115-23 PMID: 2591370
  48. Increases in tyrosine phosphorylation are detectable before phospholipase C activation after T cell receptor stimulation.
    J Immunol. 1990 Mar 1;144(5):1591-9 PMID: 1689750
  49. T cell antigen receptor-mediated activation of phospholipase C requires tyrosine phosphorylation.
    Science. 1990 Mar 30;247(4950):1584-7 PMID: 2138816
  50. Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor.
    Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358-62 PMID: 2190221
  51. Structural mutations of the T cell receptor zeta chain and its role in T cell activation.
    Science. 1990 Jul 13;249(4965):174-7 PMID: 2371564
  52. Cross-linking and conformational change in T-cell receptors: role in activation and in repertoire selection.
    Cold Spring Harb Symp Quant Biol. 1989;54 Pt 2:657-66 PMID: 2701215
  53. Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction.
    Proc Natl Acad Sci U S A. 1990 Oct;87(19):7722-6 PMID: 2217205
  54. Molecular associations on the T cell surface correlate with immunological memory.
    Eur J Immunol. 1990 Oct;20(10):2249-57 PMID: 1978709
  55. Increase of the catalytic activity of phospholipase C-gamma 1 by tyrosine phosphorylation.
    Science. 1990 Nov 30;250(4985):1253-6 PMID: 1700866
  56. Oncogenes and signal transduction.
    Cell. 1991 Jan 25;64(2):281-302 PMID: 1846320
  57. Requirement for association of p56lck with CD4 in antigen-specific signal transduction in T cells.
    Cell. 1991 Feb 8;64(3):511-20 PMID: 1671341
  58. Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides.
    Cell. 1991 Mar 8;64(5):1037-46 PMID: 1900456
  59. T cell antigen receptor activation pathways: the tyrosine kinase connection.
    Cell. 1991 Mar 8;64(5):875-8 PMID: 1848158
  60. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways.
    Cell. 1991 Mar 8;64(5):891-901 PMID: 1705867
  61. Adhesion versus coreceptor function of CD4 and CD8: role of the cytoplasmic tail in coreceptor activity.
    Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2623-7 PMID: 1901411
  62. Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn).
    Cell. 1991 Apr 19;65(2):281-91 PMID: 2015626
  63. Association of CD8 with p56lck is required for early T cell signalling events.
    EMBO J. 1991 May;10(5):1201-7 PMID: 1902413
  64. CD3 stimulation causes phosphorylation of phospholipase C-gamma 1 on serine and tyrosine residues in a human T-cell line.
    Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5453-6 PMID: 1828897
  65. Biochemical identification of a direct physical interaction between the CD4:p56lck and Ti(TcR)/CD3 complexes.
    Eur J Immunol. 1991 Jul;21(7):1663-8 PMID: 1829412
  66. Functional activation of the T-cell antigen receptor induces tyrosine phosphorylation of phospholipase C-gamma 1.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5484-8 PMID: 1712101
  67. A 32-kD GTP-binding protein associated with the CD4-p56lck and CD8-p56lck T cell receptor complexes.
    Science. 1991 Oct 18;254(5030):439-41 PMID: 1925604
  68. Protein tyrosine kinase p59fyn is associated with the T cell receptor-CD3 complex in functional human lymphocytes.
    Eur J Immunol. 1992 Jan;22(1):283-6 PMID: 1530920
  69. Differential effect of interleukin 1 on naive and memory CD4+ T cells.
    Eur J Immunol. 1992 Jan;22(1):95-100 PMID: 1346115
  70. Physical association of CD4 with the T cell receptor.
    J Immunol. 1992 Feb 1;148(3):678-88 PMID: 1370513
  71. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules.
    Cell. 1992 Jan 10;68(1):83-95 PMID: 1531041
  72. p56lck association with CD4 is required for the interaction between CD4 and the TCR/CD3 complex and for optimal antigen stimulation.
    J Immunol. 1992 Apr 1;148(7):2159-62 PMID: 1532002
  73. Activation of T cells by a tyrosine kinase activation domain in the cytoplasmic tail of CD3 epsilon.
    Science. 1992 Jan 3;255(5040):79-82 PMID: 1532456
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-01-01
Pages
90-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC394782
Subset
IM
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