Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Apr 1;167(4):1391–1405. doi: 10.1084/jem.167.4.1391

Synthetic peptides as antigens and competitors in recognition by H-2- restricted cytolytic T cells specific for HLA

PMCID: PMC2188917  PMID: 3128632

Abstract

The specificity of peptide recognition by a number of Kd-restricted CTL clones specific for HLA-CW3 or HLA-A24 was investigated. The CTL clones were derived from DBA/2 (H-2d) mice immunized with syngeneic P815 mouse cells transfected with genes encoding HLA-CW3 or HLA-A24 class I molecules. We had previously shown that CTL clones that lysed P815-CW3 transfectant target cells could lyse P815 (HLA-) target cells incubated with synthetic CW3 peptides corresponding to the COOH-terminal end of the alpha 2 domain. In the present study, we found that Kd-restricted CTL clones that lysed P815-A24 transfectant target cells recognized a synthetic peptide from the same region (residues 170-182) of the A24 molecule. CW3 and A24 differ by only one amino acid within this region. Recognition of CW3 or A24 peptides corresponded exactly with lysis of P815-HLA transfectants both for clones that mutually exclusively lysed CW3 or A24 transfectant target cells and for CW3/A24 crossreactive CTL clones. The latter CTL clones that lysed both CW3 and A24 transfectant target cells showed a clear preference for the peptide corresponding to the immunizing HLA allele. The homologous CW3 and A24 peptides could compete with each other for recognition, in contrast to a peptide from the same region of HLA-B7. Peptides from the corresponding region of the endogenous Kd and Dd/Ld molecules could also inhibit recognition of CW3 and A24 peptides. Competition with peptides apparently occurred at the level of the target cell. These results are consistent with a model whereby MHC class I molecules position protein fragments or peptides for specific recognition by T cells.

Full Text

The Full Text of this article is available as a PDF (958.2 KB).

Selected References

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

  1. Allen P. M., Strydom D. J., Unanue E. R. Processing of lysozyme by macrophages: identification of the determinant recognized by two T-cell hybridomas. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2489–2493. doi: 10.1073/pnas.81.8.2489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  3. Babbitt B. P., Matsueda G., Haber E., Unanue E. R., Allen P. M. Antigenic competition at the level of peptide-Ia binding. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4509–4513. doi: 10.1073/pnas.83.12.4509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barcinski M. A., Rosenthal A. S. Immune response gene control of determinant selection. I. Intramolecular mapping of the immunogenic sites on insulin recognized by guinea pig T and B cells. J Exp Med. 1977 Mar 1;145(3):726–742. doi: 10.1084/jem.145.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baumhüter S., Wallace C. J., Proudfoot A. E., Bron C., Corradin G. Multiple T cell antigenic determinants identified within a limited region of the horse cytochrome c molecule. Eur J Immunol. 1987 May;17(5):651–656. doi: 10.1002/eji.1830170511. [DOI] [PubMed] [Google Scholar]
  6. Burgert H. G., Maryanski J. L., Kvist S. "E3/19K" protein of adenovirus type 2 inhibits lysis of cytolytic T lymphocytes by blocking cell-surface expression of histocompatibility class I antigens. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1356–1360. doi: 10.1073/pnas.84.5.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Buus S., Colon S., Smith C., Freed J. H., Miles C., Grey H. M. Interaction between a "processed" ovalbumin peptide and Ia molecules. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3968–3971. doi: 10.1073/pnas.83.11.3968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Buus S., Sette A., Colon S. M., Jenis D. M., Grey H. M. Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell. 1986 Dec 26;47(6):1071–1077. doi: 10.1016/0092-8674(86)90822-6. [DOI] [PubMed] [Google Scholar]
  9. Cease K. B., Berkower I., York-Jolley J., Berzofsky J. A. T cell clones specific for an amphipathic alpha-helical region of sperm whale myoglobin show differing fine specificities for synthetic peptides. A multiview/single structure interpretation of immunodominance. J Exp Med. 1986 Nov 1;164(5):1779–1784. doi: 10.1084/jem.164.5.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cerottini J. C., Engers H. D., Macdonald H. R., Brunner T. Generation of cytotoxic T lymphocytes in vitro. I. Response of normal and immune mouse spleen cells in mixed leukocyte cultures. J Exp Med. 1974 Sep 1;140(3):703–717. doi: 10.1084/jem.140.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Corradin G., Chiller J. M. Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes. J Exp Med. 1979 Feb 1;149(2):436–447. doi: 10.1084/jem.149.2.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fink P. J., Matis L. A., McElligott D. L., Bookman M., Hedrick S. M. Correlations between T-cell specificity and the structure of the antigen receptor. Nature. 1986 May 15;321(6067):219–226. doi: 10.1038/321219a0. [DOI] [PubMed] [Google Scholar]
  13. Gomard E., Begue B., Sodoyer S., Maryanski J. L., Jordan B. R., Levy J. P. Murine cells expressing an HLA molecule are specifically lysed by HLA-restricted antiviral human T cells. Nature. 1986 Jan 9;319(6049):153–154. doi: 10.1038/319153a0. [DOI] [PubMed] [Google Scholar]
  14. Guillet J. G., Lai M. Z., Briner T. J., Buus S., Sette A., Grey H. M., Smith J. A., Gefter M. L. Immunological self, nonself discrimination. Science. 1987 Feb 20;235(4791):865–870. doi: 10.1126/science.2433769. [DOI] [PubMed] [Google Scholar]
  15. Guillet J. G., Lai M. Z., Briner T. J., Smith J. A., Gefter M. L. Interaction of peptide antigens and class II major histocompatibility complex antigens. Nature. 1986 Nov 20;324(6094):260–262. doi: 10.1038/324260a0. [DOI] [PubMed] [Google Scholar]
  16. Marglin A., Merrifield R. B. Chemical synthesis of peptides and proteins. Annu Rev Biochem. 1970;39:841–866. doi: 10.1146/annurev.bi.39.070170.004205. [DOI] [PubMed] [Google Scholar]
  17. Maryanski J. L., Accolla R. S., Jordan B. H2-restricted recognition of cloned HLA class I gene products expressed in mouse cells. J Immunol. 1986 Jun 15;136(12):4340–4347. [PubMed] [Google Scholar]
  18. Maryanski J. L., Moretta A., Jordan B., De Plaen E., Van Pel A., Boon T., Cerottini J. C. Human T cell recognition of cloned HLA class I gene products expressed on DNA transfectants of mouse mastocytoma P815. Eur J Immunol. 1985 Nov;15(11):1111–1117. doi: 10.1002/eji.1830151109. [DOI] [PubMed] [Google Scholar]
  19. Maryanski J. L., Pala P., Corradin G., Jordan B. R., Cerottini J. C. H-2-restricted cytolytic T cells specific for HLA can recognize a synthetic HLA peptide. Nature. 1986 Dec 11;324(6097):578–579. doi: 10.1038/324578a0. [DOI] [PubMed] [Google Scholar]
  20. Parham P., Clayberger C., Zorn S. L., Ludwig D. S., Schoolnik G. K., Krensky A. M. Inhibition of alloreactive cytotoxic T lymphocytes by peptides from the alpha 2 domain of HLA-A2. Nature. 1987 Feb 12;325(6105):625–628. doi: 10.1038/325625a0. [DOI] [PubMed] [Google Scholar]
  21. Plata F., Autran B., Martins L. P., Wain-Hobson S., Raphaël M., Mayaud C., Denis M., Guillon J. M., Debré P. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987 Jul 23;328(6128):348–351. doi: 10.1038/328348a0. [DOI] [PubMed] [Google Scholar]
  22. Salter R. D., Clayberger C., Lomen C. E., Krensky A. M., Parham P. In vitro mutagenesis at a single residue introduces B and T cell epitopes into a class I HLA molecule. J Exp Med. 1987 Jul 1;166(1):283–288. doi: 10.1084/jem.166.1.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schwartz R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. doi: 10.1146/annurev.iy.03.040185.001321. [DOI] [PubMed] [Google Scholar]
  24. Shimonkevitz R., Colon S., Kappler J. W., Marrack P., Grey H. M. Antigen recognition by H-2-restricted T cells. II. A tryptic ovalbumin peptide that substitutes for processed antigen. J Immunol. 1984 Oct;133(4):2067–2074. [PubMed] [Google Scholar]
  25. Thomas D. W., Hsieh K. H., Schauster J. L., Wilner G. D. Fine specificity of genetic regulation of guinea pig T lymphocyte responses to angiotensin II and related peptides. J Exp Med. 1981 Mar 1;153(3):583–594. doi: 10.1084/jem.153.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Togna A. R., Del Giudice G., Verdini A. S., Bonelli F., Pessi A., Engers H. D., Corradin G. Synthetic Plasmodium falciparum circumsporozoite peptides elicit heterogenous L3T4+ T cell proliferative responses in H-2b mice. J Immunol. 1986 Nov 1;137(9):2956–2960. [PubMed] [Google Scholar]
  27. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  28. Townsend A. R., Skehel J. J. The influenza A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T cells. J Exp Med. 1984 Aug 1;160(2):552–563. doi: 10.1084/jem.160.2.552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Winoto A., Urban J. L., Lan N. C., Goverman J., Hood L., Hansburg D. Predominant use of a V alpha gene segment in mouse T-cell receptors for cytochrome c. Nature. 1986 Dec 18;324(6098):679–682. doi: 10.1038/324679a0. [DOI] [PubMed] [Google Scholar]
  30. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]
  31. Zinkernagel R. M., Rosenthal K. L. Experiments and speculation on antiviral specificity of T and B cells. Immunol Rev. 1981;58:131–155. doi: 10.1111/j.1600-065x.1981.tb00352.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES