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. 1993 Mar 1;177(3):811–820. doi: 10.1084/jem.177.3.811

T cell receptor selection by and recognition of two class I major histocompatibility complex-restricted antigenic peptides that differ at a single position

PMCID: PMC2190943  PMID: 8436911

Abstract

Peptides derived from HLA-Cw3 and HLA-A24 within region 170-179 differ by a single substitution, at position 173, and are both presented by the class I major histocompatibility complex molecule H-2Kd for recognition by murine cytolytic T lymphocytes (CTLs). As a first approach to understand the way T cell receptors (TCRs) intact with the HLA peptides, we have analyzed the TCR selection by, and recognition of, the two HLA antigenic sites. First, we have compared the TCR repertoires selected by HLA-Cw3 and HLA-A24, not only by sequencing the TCRs carried by CTL clones isolated and grown in vitro, but also by analyzing the TCRs expressed in vivo by peritoneal exudate lymphocytes from immune animals. Second, we have compared the TCR crossrecognition of HLA-A24 by CTLs selected by HLA-Cw3 with that of HLA-Cw3 by CTLs selected by HLA-A24. The combined analysis of TCR selection by and recognition of these two related HLA antigenic sites provides evidence that the TCR beta junctional regions interact with the amino-terminal part of the HLA peptides.

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Selected References

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  1. Acha-Orbea H., Mitchell D. J., Timmermann L., Wraith D. C., Tausch G. S., Waldor M. K., Zamvil S. S., McDevitt H. O., Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell. 1988 Jul 15;54(2):263–273. doi: 10.1016/0092-8674(88)90558-2. [DOI] [PubMed] [Google Scholar]
  2. Arden B., Klotz J. L., Siu G., Hood L. E. Diversity and structure of genes of the alpha family of mouse T-cell antigen receptor. 1985 Aug 29-Sep 4Nature. 316(6031):783–787. doi: 10.1038/316783a0. [DOI] [PubMed] [Google Scholar]
  3. Barth R. K., Kim B. S., Lan N. C., Hunkapiller T., Sobieck N., Winoto A., Gershenfeld H., Okada C., Hansburg D., Weissman I. L. The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments. Nature. 1985 Aug 8;316(6028):517–523. doi: 10.1038/316517a0. [DOI] [PubMed] [Google Scholar]
  4. Becker D. M., Pattern P., Chien Y., Yokota T., Eshhar Z., Giedlin M., Gascoigne N. R., Goodnow C., Wolf R., Arai K. Variability and repertoire size of T-cell receptor V alpha gene segments. Nature. 1985 Oct 3;317(6036):430–434. doi: 10.1038/317430a0. [DOI] [PubMed] [Google Scholar]
  5. Behlke M. A., Chou H. S., Huppi K., Loh D. Y. Murine T-cell receptor mutants with deletions of beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Feb;83(3):767–771. doi: 10.1073/pnas.83.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Casanova J. L., Cerottini J. C., Matthes M., Necker A., Gournier H., Barra C., Widmann C., MacDonald H. R., Lemonnier F., Malissen B. H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity. J Exp Med. 1992 Aug 1;176(2):439–447. doi: 10.1084/jem.176.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Casanova J. L., Pannetier C., Jaulin C., Kourilsky P. Optimal conditions for directly sequencing double-stranded PCR products with sequenase. Nucleic Acids Res. 1990 Jul 11;18(13):4028–4028. doi: 10.1093/nar/18.13.4028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chothia C., Boswell D. R., Lesk A. M. The outline structure of the T-cell alpha beta receptor. EMBO J. 1988 Dec 1;7(12):3745–3755. doi: 10.1002/j.1460-2075.1988.tb03258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chou H. S., Anderson S. J., Louie M. C., Godambe S. A., Pozzi M. R., Behlke M. A., Huppi K., Loh D. Y. Tandem linkage and unusual RNA splicing of the T-cell receptor beta-chain variable-region genes. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1992–1996. doi: 10.1073/pnas.84.7.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chou H. S., Behlke M. A., Godambe S. A., Russell J. H., Brooks C. G., Loh D. Y. T cell receptor genes in an alloreactive CTL clone: implications for rearrangement and germline diversity of variable gene segments. EMBO J. 1986 Sep;5(9):2149–2155. doi: 10.1002/j.1460-2075.1986.tb04478.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Danska J. S., Livingstone A. M., Paragas V., Ishihara T., Fathman C. G. The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides. J Exp Med. 1990 Jul 1;172(1):27–33. doi: 10.1084/jem.172.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  13. Dembić Z., Haas W., Weiss S., McCubrey J., Kiefer H., von Boehmer H., Steinmetz M. Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature. 1986 Mar 20;320(6059):232–238. doi: 10.1038/320232a0. [DOI] [PubMed] [Google Scholar]
  14. Elliott J. F., Rock E. P., Patten P. A., Davis M. M., Chien Y. H. The adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes. Nature. 1988 Feb 18;331(6157):627–631. doi: 10.1038/331627a0. [DOI] [PubMed] [Google Scholar]
  15. Engel I., Hedrick S. M. Site-directed mutations in the VDJ junctional region of a T cell receptor beta chain cause changes in antigenic peptide recognition. Cell. 1988 Aug 12;54(4):473–484. doi: 10.1016/0092-8674(88)90068-2. [DOI] [PubMed] [Google Scholar]
  16. Gascoigne N. R., Chien Y., Becker D. M., Kavaler J., Davis M. M. Genomic organization and sequence of T-cell receptor beta-chain constant- and joining-region genes. Nature. 1984 Aug 2;310(5976):387–391. doi: 10.1038/310387a0. [DOI] [PubMed] [Google Scholar]
  17. Hedrick S. M., Nielsen E. A., Kavaler J., Cohen D. I., Davis M. M. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. doi: 10.1038/308153a0. [DOI] [PubMed] [Google Scholar]
  18. Imai K., Kanno M., Kimoto H., Shigemoto K., Yamamoto S., Taniguchi M. Sequence and expression of transcripts of the T-cell antigen receptor alpha-chain gene in a functional, antigen-specific suppressor-T-cell hybridoma. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8708–8712. doi: 10.1073/pnas.83.22.8708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Iwamoto A., Ohashi P. S., Pircher H., Walker C. L., Michalopoulos E. E., Rupp F., Hengartner H., Mak T. W. T cell receptor variable gene usage in a specific cytotoxic T cell response. Primary structure of the antigen-MHC receptor of four hapten-specific cytotoxic T cell clones. J Exp Med. 1987 Mar 1;165(3):591–600. doi: 10.1084/jem.165.3.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jorgensen J. L., Esser U., Fazekas de St Groth B., Reay P. A., Davis M. M. Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. Nature. 1992 Jan 16;355(6357):224–230. doi: 10.1038/355224a0. [DOI] [PubMed] [Google Scholar]
  21. Jouvin-Marche E., Hue I., Marche P. N., Liebe-Gris C., Marolleau J. P., Malissen B., Cazenave P. A., Malissen M. Genomic organization of the mouse T cell receptor V alpha family. EMBO J. 1990 Jul;9(7):2141–2150. doi: 10.1002/j.1460-2075.1990.tb07383.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kavaler J., Davis M. M., Chien Y. Localization of a T-cell receptor diversity-region element. Nature. 1984 Aug 2;310(5976):421–423. doi: 10.1038/310421a0. [DOI] [PubMed] [Google Scholar]
  23. Kaye J., Kersh G., Engel I., Hedrick S. M. Structure and specificity of the T cell antigen receptor. Semin Immunol. 1991 Sep;3(5):269–281. [PubMed] [Google Scholar]
  24. Lai M. Z., Jang Y. J., Chen L. K., Gefter M. L. Restricted V-(D)-J junctional regions in the T cell response to lambda-repressor. Identification of residues critical for antigen recognition. J Immunol. 1990 Jun 15;144(12):4851–4856. [PubMed] [Google Scholar]
  25. Malissen M., Minard K., Mjolsness S., Kronenberg M., Goverman J., Hunkapiller T., Prystowsky M. B., Yoshikai Y., Fitch F., Mak T. W. Mouse T cell antigen receptor: structure and organization of constant and joining gene segments encoding the beta polypeptide. Cell. 1984 Jul;37(3):1101–1110. doi: 10.1016/0092-8674(84)90444-6. [DOI] [PubMed] [Google Scholar]
  26. Malissen M., Trucy J., Jouvin-Marche E., Cazenave P. A., Scollay R., Malissen B. Regulation of TCR alpha and beta gene allelic exclusion during T-cell development. Immunol Today. 1992 Aug;13(8):315–322. doi: 10.1016/0167-5699(92)90044-8. [DOI] [PubMed] [Google Scholar]
  27. Martinon F., Cornille F., Gomard E., Fournie-Zaluski M. C., Abastado J. P., Roques B. P., Levy J. P. Two epitopes and one agretope map to a single HLA-A2 peptide recognized by H-2-restricted T cells. J Immunol. 1989 May 15;142(10):3489–3494. [PubMed] [Google Scholar]
  28. 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]
  29. Maryanski J. L., Pala P., Cerottini J. C., Corradin G. Synthetic peptides as antigens and competitors in recognition by H-2-restricted cytolytic T cells specific for HLA. J Exp Med. 1988 Apr 1;167(4):1391–1405. doi: 10.1084/jem.167.4.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Matis L. A. The molecular basis of T-cell specificity. Annu Rev Immunol. 1990;8:65–82. doi: 10.1146/annurev.iy.08.040190.000433. [DOI] [PubMed] [Google Scholar]
  32. Necker A., Rebaï N., Matthes M., Jouvin-Marche E., Cazenave P. A., Swarnworawong P., Palmer E., MacDonald H. R., Malissen B. Monoclonal antibodies raised against engineered soluble mouse T cell receptors and specific for V alpha 8-, V beta 2- or V beta 10-bearing T cells. Eur J Immunol. 1991 Dec;21(12):3035–3040. doi: 10.1002/eji.1830211220. [DOI] [PubMed] [Google Scholar]
  33. Pala P., Corradin G., Strachan T., Sodoyer R., Jordan B. R., Cerottini J. C., Maryanski J. L. Mapping of HLA epitopes recognized by H-2-restricted cytotoxic T lymphocytes specific for HLA using recombinant genes and synthetic peptides. J Immunol. 1988 Feb 1;140(3):871–877. [PubMed] [Google Scholar]
  34. Romero P., Corradin G., Luescher I. F., Maryanski J. L. H-2Kd-restricted antigenic peptides share a simple binding motif. J Exp Med. 1991 Sep 1;174(3):603–612. doi: 10.1084/jem.174.3.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984 Nov 1;312(5989):36–40. doi: 10.1038/312036a0. [DOI] [PubMed] [Google Scholar]
  36. Singer P. A., McEvilly R. J., Noonan D. J., Dixon F. J., Theofilopoulos A. N. Clonal diversity and T-cell receptor beta-chain variable gene expression in enlarged lymph nodes of MRL-lpr/lpr lupus mice. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7018–7022. doi: 10.1073/pnas.83.18.7018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Siu G., Kronenberg M., Strauss E., Haars R., Mak T. W., Hood L. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor. 1984 Sep 27-Oct 3Nature. 311(5984):344–350. doi: 10.1038/311344a0. [DOI] [PubMed] [Google Scholar]
  38. Sutherland R. M., Paterson Y., Scherle P. A., Gerhard W., Caton A. J. A new mouse T-cell receptor alpha chain variable region family. Immunogenetics. 1991;34(6):372–375. doi: 10.1007/BF01787487. [DOI] [PubMed] [Google Scholar]
  39. Taylor A. H., Haberman A. M., Gerhard W., Caton A. J. Structure-function relationships among highly diverse T cells that recognize a determinant from influenza virus hemagglutinin. J Exp Med. 1990 Dec 1;172(6):1643–1651. doi: 10.1084/jem.172.6.1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Toda M., Fujimoto S., Iwasato T., Takeshita S., Tezuka K., Ohbayashi T., Yamagishi H. Structure of extrachromosomal circular DNAs excised from T-cell antigen receptor alpha and delta-chain loci. J Mol Biol. 1988 Jul 20;202(2):219–231. doi: 10.1016/0022-2836(88)90453-6. [DOI] [PubMed] [Google Scholar]
  41. Townsend A., Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol. 1989;7:601–624. doi: 10.1146/annurev.iy.07.040189.003125. [DOI] [PubMed] [Google Scholar]
  42. Uematsu Y. Preferential association of alpha and beta chains of the T cell antigen receptor. Eur J Immunol. 1992 Feb;22(2):603–606. doi: 10.1002/eji.1830220247. [DOI] [PubMed] [Google Scholar]
  43. Wilson R. K., Lai E., Concannon P., Barth R. K., Hood L. E. Structure, organization and polymorphism of murine and human T-cell receptor alpha and beta chain gene families. Immunol Rev. 1988 Jan;101:149–172. doi: 10.1111/j.1600-065x.1988.tb00736.x. [DOI] [PubMed] [Google Scholar]
  44. Winoto A., Mjolsness S., Hood L. Genomic organization of the genes encoding mouse T-cell receptor alpha-chain. 1985 Aug 29-Sep 4Nature. 316(6031):832–836. doi: 10.1038/316832a0. [DOI] [PubMed] [Google Scholar]
  45. Yague J., Blackman M., Born W., Marrack P., Kappler J., Palmer E. The structure of V alpha and J alpha segments in the mouse. Nucleic Acids Res. 1988 Dec 9;16(23):11355–11364. doi: 10.1093/nar/16.23.11355. [DOI] [PMC free article] [PubMed] [Google Scholar]

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