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. 1980 Sep 1;152(3):620–632. doi: 10.1084/jem.152.3.620

Nature of T lymphocyte recognition of macrophage-associated antigens. V. Contribution of individual peptide residues of human fibrinopeptide B to T lymphocyte responses

PMCID: PMC2185931  PMID: 6157771

Abstract

Guinea pig T lymphocyte responses to a decapeptide antigen (NH1-Asp5- Ans6-Glu7-Glu8-Gly9-Phe10-Phe11-Ser12-Ala13-Arg14-OH) of human fibrinopeptide B (hFPB) were examined using various synthetic peptide analogues containing single residue substitutions. Each analogue was examined for antigenicity as determined by an in vitro proliferative responses of hFPN-immune strain 2 guinae pig T cells. In addition, both strain 2 and strain 13 animals were immunized with each analogue and immunogenicity assessed by in vitro T cell-proliferative responses with the homologous immunizing analogue and the parent peptide. Replacement of arginine14 with lysine formed an immunogenic analogue which showed no antigenic cross-reactivity with the native peptide in strain 2 T cell responses. In addition, substitution of arginine14 with blocked lysine again produced a unique immunogenic analogue that showed little or no antigenic identity with the intact lysine analogue or the native peptide. In similar fashion, substitution of resideu phenylalanie10 with tyrosine or Phe(4-NO2) created unique immunogenic analogues with little or no antigenic identity to the native peptide with strain 2 T cells. By contrast, replacement of phenylalanine11 with either tyrosine or Phe(4-NO2) resulted in analogues with a total loss of immunogenicity and antigenicity in strain 2 T cell responses. An analogue in which glutamic acid7,8 were replaced with glutamine retained a small degree of antigenicity with hFPB-immune T cells, but T cells from strain 2 animals immunized with the Gln analogue responded only marginally to the Gln analogue while producing good proliferative responses with the native peptide. On the other hand, an analogue in which asparatic acid5 was replaced with asparagine retained most of the antigenic identity with hFPB for strain 2 T cell responses. None of thee analogues were immunogenic for strain 13 guinea pigs. These observations are discussed with respect to the contribution of each substituted residue to T cell respones, mechanism of Ir gene function, and a model for T cell recognition of small peptide antigens.

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Selected References

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

  1. Anfinsen C. B., Ontjes D., Ohno M., Corley L., Eastlake A. The synthesis of protected peptide fragments of a staphylococcal nuclease. Proc Natl Acad Sci U S A. 1967 Oct;58(4):1806–1811. doi: 10.1073/pnas.58.4.1806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Green I., Paul W. E., Benacerraf B. Genetic control of immunological responsiveness in guinea pigs to 2,4-dinitrophenyl conjugates of poly-L-arginine, protamine, and poly-L-ornithine. Proc Natl Acad Sci U S A. 1969 Nov;64(3):1095–1102. doi: 10.1073/pnas.64.3.1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Marrack P., Kappler J. W. The role of H-2-linked genes in helper T-cell function. III. Expression of immune response genes for trinitrophenyl conjugates of poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys in B cells and macrophages. J Exp Med. 1978 Jun 1;147(6):1596–1610. doi: 10.1084/jem.147.6.1596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Miller J. F., Vadas M. A., Whitelaw A., Gamble J. Role of major histocompatibility complex gene products in delayed-type hypersensitivity. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2486–2490. doi: 10.1073/pnas.73.7.2486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Rosenthal A. S., Shevach E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Schlossman S. F., Yaron A., Ben-Efraim S., Sober H. A. Immunogenicity of a series of alpha,N-DNP-L-lysines. Biochemistry. 1965 Aug;4(8):1638–1645. doi: 10.1021/bi00884a028. [DOI] [PubMed] [Google Scholar]
  10. Schwartz B. D., Gordon D., Thomas D. W. Further chemical characterization of guinea pig Ia molecules derived from the three major classes of immunocompetent cells. Mol Immunol. 1979 Jan;16(1):43–49. doi: 10.1016/0161-5890(79)90026-9. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Seeger R. C., Oppenheim J. J. Synergistic interaction of macrophages and lymphocytes in antigen-induced transformation of lymphocytes. J Exp Med. 1970 Jul 1;132(1):44–65. doi: 10.1084/jem.132.1.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shevach E. M., Rosenthal A. S. Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response. J Exp Med. 1973 Nov 1;138(5):1213–1229. doi: 10.1084/jem.138.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shevach E. M. The function of macrophages in antigen recognition by guinea pig T lymphocytes. III. Genetic analysis of the antigens mediating macrophage-T lymphocyte interaction. J Immunol. 1976 May;116(5):1482–1489. [PubMed] [Google Scholar]
  15. Singer A., Cowing C., Hathcock K. S., Dickler H. B., Hodes R. J. Cellular and genetic control of antibody responses in vitro. III. Immune response gene regulation of accessory cell function. J Exp Med. 1978 Jun 1;147(6):1611–1620. doi: 10.1084/jem.147.6.1611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sprent J. Restricted helper function of F1 hybrid T cells positively selected to heterologous erythrocytes in irradiated parental strain mice. II. Evidence for restrictions affecting helper cell induction and T-B collaboration, both mapping to the K-end of the H-2 complex. J Exp Med. 1978 Apr 1;147(4):1159–1174. doi: 10.1084/jem.147.4.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Stashenko P. P., Schlossman S. F. Antigen recognition: the specificity of an isolated T lymphocyte population. J Immunol. 1977 Feb;118(2):544–550. [PubMed] [Google Scholar]
  18. Stulbarg M., Schlossman S. F. The specificity of antigen-induced thymidine-2-14C incorporation into lymph node cells frrom sensitized animals. J Immunol. 1968 Oct;101(4):764–769. [PubMed] [Google Scholar]
  19. 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]
  20. Thomas D. W., Meltz S. K., Wilner G. D. Nature of T lymphocyte recognition of macrophage-associated antigens. II. Macrophage determination of guinea pig T cell responses to human fibrinopeptide B. J Immunol. 1979 Sep;123(3):1299–1302. [PubMed] [Google Scholar]
  21. Thomas D. W., Shevach E. M. Nature of the antigenic complex recognized by T lymphocytes: specific sensitization by antigens associated with allogeneic macrophages. Proc Natl Acad Sci U S A. 1977 May;74(5):2104–2108. doi: 10.1073/pnas.74.5.2104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Waldron J. A., Jr, Horn R. G., Rosenthal A. S. Antigen-induced proliferation of guinea pig lymphocytes in vitro: obligatory role of macrophages in the recognition of antigen by immune T-lymphocytes. J Immunol. 1973 Jul;111(1):58–64. [PubMed] [Google Scholar]
  23. Wilner G. D., Nossel H. L., Canfield R. E., Butler V. P., Jr Immunochemical studies of human fibrinopeptide A using synthetic peptide homologues. Biochemistry. 1976 Mar 23;15(6):1209–1213. doi: 10.1021/bi00651a005. [DOI] [PubMed] [Google Scholar]
  24. Wilner G. D., Thomas D. W., Nossel H. L., Robbins P. F., Mudd M. S. Immunochemical analysis of rabbit antihuman fibrinopeptide B antibodies. Biochemistry. 1979 Nov 13;18(23):5078–5082. doi: 10.1021/bi00590a009. [DOI] [PubMed] [Google Scholar]
  25. Yaron A., Dunham E. K., 3rd, Schlossman S. F. Synthesis and immunological properties of the oligolysyl-N-epsilon-dinitrophenyllysine and oligolysylalanylalanylalanyl-N-epsilon-dinitrophenyllysine peptide series. Biochemistry. 1974 Jan 15;13(2):347–354. doi: 10.1021/bi00699a020. [DOI] [PubMed] [Google Scholar]
  26. Zinkernagel R. M., Doherty P. C. H-2 compatability requirement for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. Different cytotoxic T-cell specificities are associated with structures coded for in H-2K or H-2D;. J Exp Med. 1975 Jun 1;141(6):1427–1436. doi: 10.1084/jem.141.6.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]

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