T-lymphocyte response to cytochrome c. I. Demonstration of a T-cell heteroclitic proliferative response and identification of a topographic antigenic determinant on pigeon cytochrome c whose immune recognition requires two complementing major histocompatibility complex-linked immune response genes
- PMID: 92520
- PMCID: PMC2185679
- DOI: 10.1084/jem.150.4.830
T-lymphocyte response to cytochrome c. I. Demonstration of a T-cell heteroclitic proliferative response and identification of a topographic antigenic determinant on pigeon cytochrome c whose immune recognition requires two complementing major histocompatibility complex-linked immune response genes
Abstract
The T-lymphocyte proliferative response to pigeon cytochrome c was studied in the mouse. H-2a and H-2k strains were responders to this antigen whereas H-2b, H-2d, H-2f, H-2ja, H-2p, H-2q, H-2r, H-2s, and H-2u strains were low or nonresponders. Genetic mapping demonstrated that two major histocompatibility complex (MHC)-linked Ir genes control the response, one in I-A, the other in I-E/I-C. The major antigenic determinant recognized in this response was localized by cross-stimulations with species variants and cyanogen bromide cleavage fragments of cytochrome c. It was found to be a topographic surface determinant composed of an isoleucine for valine substitution at residue 3, a glutamine for lysine substitution at residue 100 and a lysine for glutamic acid substitution at residue 104. Tobacco hornworm moth cytochrome c, which contains a glutamine at residue 100 but a terminal lysine at residue 103 (one amino acid closer to the glutamine), stimulated pigeon cytochrome c immune T cells better than the immunogen. This result demonstrates for the first time a functional T-cell heteroclitic proliferative response in a system under Ir gene control. Immunization with the cyanogen bromide cleavage fragments revealed that only pigeon cytochrome c fragment 81-104 was immunogenic. This fragment primed for a T-cell proliferative response whose specificity was nearly identical to that of the T-cell response primed for by the whole molecule, suggesting that the glutamine at 100 and the lysine at 104 form the immunodominant portion of the antigenic site. Furthermore, mixing experiments using the two cross-reacting antigens, hippopotamus cytochrome c and Pekin duck or chicken cytochrome c fragment (81-104), each of which contains only one of the two immunodominant substitutions, demonstrated that the T lymphocytes responding to the major antigenic determinant comprise a single family of clones that recognize both amino acids as part of the same determinant. Thus, two complementing MHC-linked Ir genes can control the immune response to a single antigenic determinant.
Similar articles
-
Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in Ae:E alpha complex expression causes a corresponding defect in antigen-presenting cell function.J Exp Med. 1982 Feb 1;155(2):508-23. doi: 10.1084/jem.155.2.508. J Exp Med. 1982. PMID: 6173457 Free PMC article.
-
Genetic control of the T-lymphocyte proliferative response to cytochrome c.Adv Exp Med Biol. 1978;98:371-86. doi: 10.1007/978-1-4615-8858-0_20. Adv Exp Med Biol. 1978. PMID: 82388
-
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):319-24. J Immunol. 1983. PMID: 6190913
-
Ir1 genes, peripheral cross-tolerance and immunodominance in MHC class I-restricted T-cell responses: an old quagmire revisited.Immunol Rev. 1993 Jun;133:75-91. doi: 10.1111/j.1600-065x.1993.tb01510.x. Immunol Rev. 1993. PMID: 8225372 Review.
-
Medial histocompatibility antigens.Scand J Immunol. 1981 Dec;14(6):643-54. doi: 10.1111/j.1365-3083.1981.tb00607.x. Scand J Immunol. 1981. PMID: 6177030 Review.
Cited by
-
Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo.J Exp Med. 1987 Feb 1;165(2):302-19. doi: 10.1084/jem.165.2.302. J Exp Med. 1987. PMID: 3029267 Free PMC article.
-
The major parasite surface antigen associated with human resistance to schistosomiasis is a 37-kD glyceraldehyde-3P-dehydrogenase.J Exp Med. 1989 Dec 1;170(6):2065-80. doi: 10.1084/jem.170.6.2065. J Exp Med. 1989. PMID: 2584935 Free PMC article.
-
Mechanisms influencing the immunodominance of T cell determinants.J Exp Med. 1988 Dec 1;168(6):2091-104. doi: 10.1084/jem.168.6.2091. J Exp Med. 1988. PMID: 2462005 Free PMC article.
-
Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in Ae:E alpha complex expression causes a corresponding defect in antigen-presenting cell function.J Exp Med. 1982 Feb 1;155(2):508-23. doi: 10.1084/jem.155.2.508. J Exp Med. 1982. PMID: 6173457 Free PMC article.
-
A possible immunodominant epitope recognized by murine T lymphocytes immune to different myoglobins.Proc Natl Acad Sci U S A. 1982 Aug;79(15):4723-7. doi: 10.1073/pnas.79.15.4723. Proc Natl Acad Sci U S A. 1982. PMID: 6181511 Free PMC article.
References
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials