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. 1985 Jul 1;162(1):332–345. doi: 10.1084/jem.162.1.332

Distinct recognition phenotypes exist for T cell clones specific for small peptide regions of proteins. Implications for the mechanisms underlying major histocompatibility complex-restricted antigen recognition and clonal deletion models of immune response gene defects

PMCID: PMC2187680  PMID: 2409209

Abstract

Using synthetic peptides as antigens, it was found that T cell clones of a given haplotype specific for 13-16 amino acid peptides could be clearly distinguished by the varied influence of amino acid substitutions on recognition. This was true for different antigenic determinants within peptides 81-96 and 74-86 of hen egg-white lysozyme, recognized in the context of the I-Ab and I-Ak molecules, respectively. Considerable complexity was demonstrated in the induced T cell repertoire specific for apparently single determinants, which implies that diversity of T cell recognition approaches that for B cells. The implications of the degeneracy of T cell recognition are discussed in the context of mechanisms through which Ia molecules restrict recognition and theories of Ir gene defects.

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Selected References

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  1. Adorini L., Harvey M. A., Miller A., Sercarz E. E. Fine specificity of regulatory T cells. II. Suppressor and helper T cells are induced by different regions of hen egg-white lysozyme in a genetically nonresponder mouse strain. J Exp Med. 1979 Aug 1;150(2):293–306. doi: 10.1084/jem.150.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beck B. N., Nelson P. A., Fathman C. G. The I-Ab mutant B6.C-H-2bm12 allows definition of multiple T cell epitopes on I-A molecules. J Exp Med. 1983 May 1;157(5):1396–1404. doi: 10.1084/jem.157.5.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  4. Benjamin D. C., Berzofsky J. A., East I. J., Gurd F. R., Hannum C., Leach S. J., Margoliash E., Michael J. G., Miller A., Prager E. M. The antigenic structure of proteins: a reappraisal. Annu Rev Immunol. 1984;2:67–101. doi: 10.1146/annurev.iy.02.040184.000435. [DOI] [PubMed] [Google Scholar]
  5. Glimcher L. H., Hamano T., Asofsky R., Sachs D. H., Pierres M., Samelson L. E., Sharrow S. O., Paul W. E. IA mutant functional antigen-presenting cell lines. J Immunol. 1983 May;130(5):2287–2294. [PubMed] [Google Scholar]
  6. Goverman J., Minard K., Shastri N., Hunkapiller T., Hansburg D., Sercarz E., Hood L. Rearranged beta T cell receptor genes in a helper T cell clone specific for lysozyme: no correlation between V beta and MHC restriction. Cell. 1985 Apr;40(4):859–867. doi: 10.1016/0092-8674(85)90345-9. [DOI] [PubMed] [Google Scholar]
  7. Hackett C. J., Dietzschold B., Gerhard W., Ghrist B., Knorr R., Gillessen D., Melchers F. Influenza virus site recognized by a murine helper T cell specific for H1 strains. Localization to a nine amino acid sequence in the hemagglutinin molecule. J Exp Med. 1983 Aug 1;158(2):294–302. doi: 10.1084/jem.158.2.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hansburg D., Fairwell T., Schwartz R. H., Appella E. The T lymphocyte response to cytochrome c. IV. Distinguishable sites on a peptide antigen which affect antigenic strength and memory. J Immunol. 1983 Jul;131(1):319–324. [PubMed] [Google Scholar]
  9. Heber-Katz E., Hansburg D., Schwartz R. H. The Ia molecule of the antigen-presenting cell plays a critical role in immune response gene regulation of T cell activation. J Mol Cell Immunol. 1983;1(1):3–18. [PubMed] [Google Scholar]
  10. Hertel-Wulff B., Goodman J. W., Fathman C. G., Lewis G. K. Arsonate-specific murine T cell clones. I. Genetic control and antigen specificity. J Exp Med. 1983 Mar 1;157(3):987–997. doi: 10.1084/jem.157.3.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hochman P. S., Huber B. T. Immune recognition of insulin by H-2b mice: the mutation in the I-Ab beta gene of the B6.C-H-2bm12 mouse alters the self-I-A-restricted T cell repertoire. Eur J Immunol. 1984 Jul;14(7):610–615. doi: 10.1002/eji.1830140706. [DOI] [PubMed] [Google Scholar]
  12. Jensen P. E., Pierce C. W., Kapp J. A. Regulatory mechanisms in immune responses to heterologous insulins. II. Suppressor T cell activation associated with nonresponsiveness in H-2b mice. J Exp Med. 1984 Oct 1;160(4):1012–1026. doi: 10.1084/jem.160.4.1012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Katz M. E., Maizels R. M., Wicker L., Miller A., Sercarz E. E. Immunological focusing by th mouse major histocompatibility complex: mouse strains confronted with distantly related lysozymes confine their attention to very few epitopes. Eur J Immunol. 1982 Jul;12(7):535–540. doi: 10.1002/eji.1830120702. [DOI] [PubMed] [Google Scholar]
  15. Kimoto M., Fathman C. G. Antigen-reactive T cell clones. I. Transcomplementing hybrid I-A-region gene products function effectively in antigen presentation. J Exp Med. 1980 Oct 1;152(4):759–770. doi: 10.1084/jem.152.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maizels R. M., Clarke J. A., Harvey M. A., Miller A., Sercarz E. E. Epitope specificity of the T cell proliferative response to lysozyme: proliferative T cells react predominantly to different determinants from those recognized by B cells. Eur J Immunol. 1980 Jul;10(7):509–515. doi: 10.1002/eji.1830100705. [DOI] [PubMed] [Google Scholar]
  17. Maizels R. M., Clarke J. A., Harvey M. A., Miller A., Sercarz E. E. Ir-gene control of T cell proliferative responses: two distinct expressions of the genetically nonresponsive state. Eur J Immunol. 1980 Jul;10(7):516–520. doi: 10.1002/eji.1830100706. [DOI] [PubMed] [Google Scholar]
  18. Manca F., Clarke J. A., Miller A., Sercarz E. E., Shastri N. A limited region within hen egg-white lysozyme serves as the focus for a diversity of T cell clones. J Immunol. 1984 Oct;133(4):2075–2078. [PubMed] [Google Scholar]
  19. Marrack P., Shimonkevitz R., Hannum C., Haskins K., Kappler J. The major histocompatibility complex-restricted antigen receptor on T cells. IV. An antiidiotypic antibody predicts both antigen and I-specificity. J Exp Med. 1983 Nov 1;158(5):1635–1646. doi: 10.1084/jem.158.5.1635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Matzinger P. A one-receptor view of T-cell behaviour. Nature. 1981 Aug 6;292(5823):497–501. doi: 10.1038/292497a0. [DOI] [PubMed] [Google Scholar]
  21. Needleman B. W., Pierres M., Devaux C. A., Dwyer P. N., Finnegan A., Sachs D. H., Hodes R. J. An analysis of functional T cell recognition sites on I-E molecules. J Immunol. 1984 Aug;133(2):589–596. [PubMed] [Google Scholar]
  22. Oki A., Sercarz E. T cell tolerance studied at the level of antigenic determinants. I. Latent reactivity to lysozyme peptides that lack suppressogenic epitopes can be revealed in lysozyme-tolerant mice. J Exp Med. 1985 May 1;161(5):897–911. doi: 10.1084/jem.161.5.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pincus M. R., Gerewitz F., Schwartz R. H., Scheraga H. A. Correlation between the conformation of cytochrome c peptides and their stimulatory activity in a T-lymphocyte proliferation assay. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3297–3300. doi: 10.1073/pnas.80.11.3297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rock K. L., Benacerraf B. MHC-restricted T cell activation: analysis with T cell hybridomas. Immunol Rev. 1983;76:29–57. doi: 10.1111/j.1600-065x.1983.tb01096.x. [DOI] [PubMed] [Google Scholar]
  25. Rosenthal A. S. Determinant selection and macrophage function in genetic control of the immune response. Immunol Rev. 1978;40:136–152. doi: 10.1111/j.1600-065x.1978.tb00404.x. [DOI] [PubMed] [Google Scholar]
  26. Samelson L. E., Schwartz R. H. T cell clone-specific alloantisera that inhibit or stimulate antigen-induced T cell activation. J Immunol. 1983 Dec;131(6):2645–2650. [PubMed] [Google Scholar]
  27. Schwartz R. H. A clonal deletion model for Ir gene control of the immune response. Scand J Immunol. 1978;7(1):3–10. doi: 10.1111/j.1365-3083.1978.tb00420.x. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Schwartz R. H., Yano A., Paul W. E. Interaction between antigen-presenting cells and primed T lymphocytes: an assessment of Ir gene expression in the antigen-presenting cell. Immunol Rev. 1978;40:153–180. doi: 10.1111/j.1600-065x.1978.tb00405.x. [DOI] [PubMed] [Google Scholar]
  30. Shastri N., Miller A., Sercarz E. E. The expressed T cell repertoire is hierarchical: the precise focus of lysozyme-specific T cell clones is dependent upon the structure of the immunogen. J Mol Cell Immunol. 1984;1(6):369–379. [PubMed] [Google Scholar]
  31. 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]
  32. Thomas D. W., Meltz S. K., Wilner G. D. Nature of T lymphocyte recognition of macrophage-associated antigens. I. Response of guinea pig T cells to human fibrinopeptide B. J Immunol. 1979 Aug;123(2):759–764. [PubMed] [Google Scholar]

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