Abstract
The genetic control of the cytotoxic T-cell response to the male histocompatibility antigen, H-Y, was analyzed in BALB/cKe(C) and SJL/J(J) which are both nonresponders. However, the (C X J)F1 hybrid is a responder. Therefore, two dominant complementing genes are involved. Analysis of a set of (C X J) recombinant inbred (RI) lines reveals that these two complementing gene products are a restricting element (R) encoded by the H-2 (MHC) locus on chromosome 17 and a subunit of the T- cell receptor (anti-R) encoded by the Tar alpha-locus on chromosome 14. The order and orientation of gene segments within the Tar alpha-locus has also been established relative to the chromosome 14 marker, Es-10. The existence of two RI strains which are recombinant at chromosome 14 has made it possible to determine that this order is Es-10--v alpha-1-- v alpha-2--[C alpha--Np-2]--centromere. The implications of these data for the antigen-specific regulation of immune responsiveness are discussed in terms of the dual recognitive-single receptor model.
Full Text
The Full Text of this article is available as a PDF (1.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Behlke M. A., Spinella D. G., Chou H. S., Sha W., Hartl D. L., Loh D. Y. T-cell receptor beta-chain expression: dependence on relatively few variable region genes. Science. 1985 Aug 9;229(4713):566–570. doi: 10.1126/science.3875151. [DOI] [PubMed] [Google Scholar]
- Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohn M. The T-cell receptor mediating restrictive recognition of antigen. Cell. 1983 Jul;33(3):657–669. doi: 10.1016/0092-8674(83)90009-0. [DOI] [PubMed] [Google Scholar]
- Collins M. K., Owen M. J. The T cell antigen receptor. Biochem J. 1985 Sep 1;230(2):281–291. doi: 10.1042/bj2300281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cory S., Adams J. M. Deletions are associated with somatic rearrangement of immunoglobulin heavy chain genes. Cell. 1980 Jan;19(1):37–51. doi: 10.1016/0092-8674(80)90386-4. [DOI] [PubMed] [Google Scholar]
- Dembić Z., Bannwarth W., Taylor B. A., Steinmetz M. The gene encoding the T-cell receptor alpha-chain maps close to the Np-2 locus on mouse chromosome 14. Nature. 1985 Mar 21;314(6008):271–273. doi: 10.1038/314271a0. [DOI] [PubMed] [Google Scholar]
- Epstein R., Lehmann K., Cohn M. Induction of lambda 1-immunoglobulin is determined by a regulatory gene (r lambda 1) linked (or identical) to the structural (c lambda 1) gene. J Exp Med. 1983 May 1;157(5):1681–1686. doi: 10.1084/jem.157.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Epstein R., Roehm N., Marrack P., Kappler J., Davis M., Hedrick S., Cohn M. Genetic markers of the antigen-specific T cell receptor locus. J Exp Med. 1985 May 1;161(5):1219–1224. doi: 10.1084/jem.161.5.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fierz W., Farmer G. A., Sheena J. H., Simpson E. Genetic analysis of the non-H-2-linked Ir genes controlling the cytotoxic T-cell response to H-Y in H-2d mice. Immunogenetics. 1982;16(6):593–601. doi: 10.1007/BF00372028. [DOI] [PubMed] [Google Scholar]
- 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]
- Hurme M., Hetherington C. M., Chandler P. R., Simpson E. Cytotoxic T-cell responses to H-Y: mapping of the Ir genes. J Exp Med. 1978 Mar 1;147(3):758–767. doi: 10.1084/jem.147.3.758. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kranz D. M., Saito H., Heller M., Takagaki Y., Haas W., Eisen H. N., Tonegawa S. Limited diversity of the rearranged T-cell gamma gene. 1985 Feb 28-Mar 6Nature. 313(6005):752–755. doi: 10.1038/313752a0. [DOI] [PubMed] [Google Scholar]
- Langman R. E., Cohn M. T cells function via restricted recognition of antigen, not antigen-restricted recognition. Cell Immunol. 1985 Sep;94(2):598–608. doi: 10.1016/0008-8749(85)90283-7. [DOI] [PubMed] [Google Scholar]
- Maniatis T., Jeffrey A., Kleid D. G. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. doi: 10.1073/pnas.72.3.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pernis B., Axel R. A one and a half receptor model for MHC-restricted antigen recognition by T lymphocytes. Cell. 1985 May;41(1):13–16. doi: 10.1016/0092-8674(85)90053-4. [DOI] [PubMed] [Google Scholar]
- Sakano T., Wilbur S. M., Bonavida B., Cohn M. Non-H-2-linked control of in vivo growth of SJL/J-derived reticulum cell sarcoma in recombinant inbred strains between BALB/cKe and SJL/J mice. J Natl Cancer Inst. 1985 Oct;75(4):669–673. [PubMed] [Google Scholar]
- 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]
- Skow L. C., Donner M. E. The locus encoding alpha A-crystallin is closely linked to H-2K on mouse chromosome 17. Genetics. 1985 Aug;110(4):723–732. doi: 10.1093/genetics/110.4.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White J., Haskins K. M., Marrack P., Kappler J. Use of I region-restricted, antigen-specific T cell hybridomas to produce idiotypically specific anti-receptor antibodies. J Immunol. 1983 Mar;130(3):1033–1037. [PubMed] [Google Scholar]
- Wikstrand C. J., Haughton G., Bailey D. W. The male antigen. II. Regulation of the primary and secondary responses to H-Y by H-2 associated genes. Cell Immunol. 1974 Feb;10(2):238–247. doi: 10.1016/0008-8749(74)90115-4. [DOI] [PubMed] [Google Scholar]
- Womack J. E., Davisson M. T., Eicher E. M., Kendall D. A. Mapping of nucleoside phosphorylase (Np-1) and esterase 10 (Es-10) on mouse chromosome 14. Biochem Genet. 1977 Apr;15(3-4):347–355. doi: 10.1007/BF00484465. [DOI] [PubMed] [Google Scholar]
- Yagüe J., White J., Coleclough C., Kappler J., Palmer E., Marrack P. The T cell receptor: the alpha and beta chains define idiotype, and antigen and MHC specificity. Cell. 1985 Aug;42(1):81–87. doi: 10.1016/s0092-8674(85)80103-3. [DOI] [PubMed] [Google Scholar]
- von Boehmer H., Turton K., Haas W. The role of the left end of the H-2b haplotype in the male-specific cytotoxic T cell response. Eur J Immunol. 1979 Nov;9(11):913–915. doi: 10.1002/eji.1830091115. [DOI] [PubMed] [Google Scholar]