Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Oct 1;172(4):1267–1270. doi: 10.1084/jem.172.4.1267

Analysis of T cell signaling by class I MHC molecules: the cytoplasmic domain is not required for signal transduction

PMCID: PMC2188606  PMID: 2212953

Abstract

The structural requirements for signal transduction by class I major histocompatibility complex (MHC) molecules were examined. Native or mutant HLA-A2 or HLA-B27 constructs lacking most of their cytoplasmic domains were co-transfected with pSV2neo into Jurkat cells. Transfection of either native or mutant constructs resulted in a comparable expression of the gene products. Stimulation of transfectants expressing either native or truncated A2 or B27 molecules with specific mAb evoked an increase in [Ca2+]i upon crosslinking. Moreover, crosslinking native or truncated A2 or B27 induced IL-2 production upon co-stimulation with phorbol myristate acetate. These results confirm that crosslinking class I MHC molecules transduces an activation signal to human T cells. Effective signaling was observed when all but four of the intracytoplasmic residues were deleted, indicating that signal transduction does not require this portion of the molecule.

Full Text

The Full Text of this article is available as a PDF (326.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chang H. C., Moingeon P., Lopez P., Krasnow H., Stebbins C., Reinherz E. L. Dissection of the human CD2 intracellular domain. Identification of a segment required for signal transduction and interleukin 2 production. J Exp Med. 1989 Jun 1;169(6):2073–2083. doi: 10.1084/jem.169.6.2073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Geppert T. D., Wacholtz M. C., Davis L. S., Lipsky P. E. Activation of human T4 cells by cross-linking class I MHC molecules. J Immunol. 1988 Apr 1;140(7):2155–2164. [PubMed] [Google Scholar]
  3. Geppert T. D., Wacholtz M. C., Patel S. S., Lightfoot E., Lipsky P. E. Activation of human T cell clones and Jurkat cells by cross-linking class I MHC molecules. J Immunol. 1989 Jun 1;142(11):3763–3772. [PubMed] [Google Scholar]
  4. Guild B. C., Erikson R. L., Strominger J. L. HLA-A2 and HLA-B7 antigens are phosphorylated in vitro by rous sarcoma virus kinase (pp60v-src) at a tyrosine residue encoded in a highly conserved exon of the intracellular domain. Proc Natl Acad Sci U S A. 1983 May;80(10):2894–2898. doi: 10.1073/pnas.80.10.2894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Guild B. C., Strominger J. L. Human and murine class I MHC antigens share conserved serine 335, the site of HLA phosphorylation in vivo. J Biol Chem. 1984 Jul 25;259(14):9235–9240. [PubMed] [Google Scholar]
  6. He Q., Beyers A. D., Barclay A. N., Williams A. F. A role in transmembrane signaling for the cytoplasmic domain of the CD2 T lymphocyte surface antigen. Cell. 1988 Sep 23;54(7):979–984. doi: 10.1016/0092-8674(88)90112-2. [DOI] [PubMed] [Google Scholar]
  7. McMichael A. J., Parham P., Rust N., Brodsky F. A monoclonal antibody that recognizes an antigenic determinant shared by HLA A2 and B17. Hum Immunol. 1980 Sep;1(2):121–129. doi: 10.1016/0198-8859(80)90099-3. [DOI] [PubMed] [Google Scholar]
  8. Murre C., Reiss C. S., Bernabeu C., Chen L. B., Burakoff S. J., Seidman J. G. Construction, expression and recognition of an H-2 molecule lacking its carboxyl terminus. Nature. 1984 Feb 2;307(5950):432–436. doi: 10.1038/307432a0. [DOI] [PubMed] [Google Scholar]
  9. Nabavi N., Ghogawala Z., Myer A., Griffith I. J., Wade W. F., Chen Z. Z., McKean D. J., Glimcher L. H. Antigen presentation abrogated in cells expressing truncated Ia molecules. J Immunol. 1989 Mar 1;142(5):1444–1447. [PubMed] [Google Scholar]
  10. Parham P., Bodmer W. F. Monoclonal antibody to a human histocompatibility alloantigen, HLA-A2. Nature. 1978 Nov 23;276(5686):397–399. doi: 10.1038/276397a0. [DOI] [PubMed] [Google Scholar]
  11. Taurog J. D., el-Zaatari F. A. In vitro mutagenesis of HLA-B27. Substitution of an unpaired cysteine residue in the alpha 1 domain causes loss of antibody-defined epitopes. J Clin Invest. 1988 Sep;82(3):987–992. doi: 10.1172/JCI113708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Thurau S. R., Wildner G., Kuon W., Weiss E. H., Riethmüller G. Expression and immunogenicity of HLA-B27 in high-transfection recipient P815: a new method to induce monoclonal antibodies directed against HLA-B27. Tissue Antigens. 1989 May;33(5):511–519. doi: 10.1111/j.1399-0039.1989.tb01702.x. [DOI] [PubMed] [Google Scholar]
  13. Vega M. A., Strominger J. L. Constitutive endocytosis of HLA class I antigens requires a specific portion of the intracytoplasmic tail that shares structural features with other endocytosed molecules. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2688–2692. doi: 10.1073/pnas.86.8.2688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES