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. 1989 Oct 1;170(4):1059–1073. doi: 10.1084/jem.170.4.1059

Analysis of Mlsc genetics. A novel instance of genetic redundancy

PMCID: PMC2189471  PMID: 2477483

Abstract

The identity of the self determinants involved in the selection of the T cell repertoire has been a matter of considerable interest. In addition to the apparent critical role of MHC gene products, accumulated experimental results indicate the importance of non-MHC gene products in T cell repertoire selection. In particular, murine Mlsa and Mlsc determinants have been shown to be highly stimulatory to allogeneic T cells and to be involved in the negative selection (elimination) of self-reactive T cells expressing selected TCR V beta segments. In this work, a unique phenomenon of genetic redundancy is described in the control of Mlsc expression: Mlsc appears to be controlled by at least two unlinked loci, and the product of either one of these loci is sufficient to evoke Mlsc-specific T cell response and to act as a ligand in the deletion of self Mlsc-reactive V beta 3+ T cells. Based on these findings, we propose a possible explanation for the fact that Mls-like genes or gene products have not been identified in other species such as man.

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Selected References

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

  1. Abe R., Hodes R. J. T-cell recognition of minor lymphocyte stimulating (Mls) gene products. Annu Rev Immunol. 1989;7:683–708. doi: 10.1146/annurev.iy.07.040189.003343. [DOI] [PubMed] [Google Scholar]
  2. Abe R., Hodes R. J. The Mls system: non-MHC genes that encode strong T-cell stimulatory determinants. Immunol Today. 1988 Jul-Aug;9(7-8):230–235. doi: 10.1016/0167-5699(88)91221-2. [DOI] [PubMed] [Google Scholar]
  3. Abe R., Ryan J. J., Finkelman F. D., Hodes R. J. T cell recognition of Mls. T cell clones demonstrate polymorphism between Mlsa, Mlsc, and Mlsd. J Immunol. 1987 Jan 15;138(2):373–379. [PubMed] [Google Scholar]
  4. Abe R., Ryan J. J., Hodes R. J. Clonal analysis of the Mls system. A reappraisal of polymorphism and allelism among Mlsa, Mlsc, and Mlsd. J Exp Med. 1987 Apr 1;165(4):1113–1129. doi: 10.1084/jem.165.4.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Abe R., Ryan J. J., Hodes R. J. Mls is not a single gene, allelic system. Different stimulatory Mls determinants are the products of at least two nonallelic, unlinked genes. J Exp Med. 1987 Oct 1;166(4):1150–1155. doi: 10.1084/jem.166.4.1150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Abe R., Vacchio M. S., Fox B., Hodes R. J. Preferential expression of the T-cell receptor V beta 3 gene by Mlsc reactive T cells. Nature. 1988 Oct 27;335(6193):827–830. doi: 10.1038/335827a0. [DOI] [PubMed] [Google Scholar]
  7. Abromson-Leeman S. R., Laning J. C., Dorf M. E. T cell recognition of Mlsc,x determinants. J Immunol. 1988 Mar 15;140(6):1726–1731. [PubMed] [Google Scholar]
  8. Bill J., Kanagawa O., Woodland D. L., Palmer E. The MHC molecule I-E is necessary but not sufficient for the clonal deletion of V beta 11-bearing T cells. J Exp Med. 1989 Apr 1;169(4):1405–1419. doi: 10.1084/jem.169.4.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  10. Click R. E., Adelmann A. Multigene control of Mlsc. Immunogenetics. 1988;28(6):412–416. doi: 10.1007/BF00355372. [DOI] [PubMed] [Google Scholar]
  11. DeKruyff R. H., Ju S. T., Laning J., Cantor H., Dorf M. E. Activation requirements of cloned inducer T cells. III. Need for two stimulator cells in the response of a cloned line to Mls determinants. J Immunol. 1986 Aug 15;137(4):1109–1114. [PubMed] [Google Scholar]
  12. Festenstein H. Immunogenetic and biological aspects of in vitro lymphocyte allotransformation (MLR) in the mouse. Transplant Rev. 1973;15:62–88. doi: 10.1111/j.1600-065x.1973.tb00111.x. [DOI] [PubMed] [Google Scholar]
  13. Finkelman F. D., Kessler S. W., Mushinski J. F., Potter M. IgD-secreting murine plasmacytomas: identification and partial characterization of two IgD myeloma proteins. J Immunol. 1981 Feb;126(2):680–687. [PubMed] [Google Scholar]
  14. Fry A. M., Matis L. A. Self-tolerance alters T-cell receptor expression in an antigen-specific MHC restricted immune response. Nature. 1988 Oct 27;335(6193):830–832. doi: 10.1038/335830a0. [DOI] [PubMed] [Google Scholar]
  15. Kappler J. W., Wade T., White J., Kushnir E., Blackman M., Bill J., Roehm N., Marrack P. A T cell receptor V beta segment that imparts reactivity to a class II major histocompatibility complex product. Cell. 1987 Apr 24;49(2):263–271. doi: 10.1016/0092-8674(87)90567-8. [DOI] [PubMed] [Google Scholar]
  16. Kronenberg M., Siu G., Hood L. E., Shastri N. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu Rev Immunol. 1986;4:529–591. doi: 10.1146/annurev.iy.04.040186.002525. [DOI] [PubMed] [Google Scholar]
  17. MacDonald H. R., Pedrazzini T., Schneider R., Louis J. A., Zinkernagel R. M., Hengartner H. Intrathymic elimination of Mlsa-reactive (V beta 6+) cells during neonatal tolerance induction to Mlsa-encoded antigens. J Exp Med. 1988 Jun 1;167(6):2005–2010. doi: 10.1084/jem.167.6.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Macphail S., Ishizaka S. T., Bykowsky M. J., Lattime E. C., Stutman O. Specific neonatally induced tolerance to Mls locus determinants. J Immunol. 1985 Nov;135(5):2967–2974. [PubMed] [Google Scholar]
  19. Marrack P., Kappler J. The T-cell repertoire for antigen and MHC. Immunol Today. 1988 Oct;9(10):308–315. doi: 10.1016/0167-5699(88)91324-2. [DOI] [PubMed] [Google Scholar]
  20. Matzinger P., Bevan M. J. Hypothesis: why do so many lymphocytes respond to major histocompatibility antigens? Cell Immunol. 1977 Mar 1;29(1):1–5. doi: 10.1016/0008-8749(77)90269-6. [DOI] [PubMed] [Google Scholar]
  21. Morrissey P. J., Bradley D., Sharrow S. O., Singer A. T cell tolerance to non-H-2-encoded stimulatory alloantigens is induced intrathymically but not prethymically. J Exp Med. 1983 Aug 1;158(2):365–377. doi: 10.1084/jem.158.2.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pullen A. M., Marrack P., Kappler J. W. Evidence that Mls-2 antigens which delete V beta 3+ T cells are controlled by multiple genes. J Immunol. 1989 May 1;142(9):3033–3037. [PubMed] [Google Scholar]
  23. Pullen A. M., Marrack P., Kappler J. W. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. doi: 10.1038/335796a0. [DOI] [PubMed] [Google Scholar]
  24. Sprent J., Webb S. R. Function and specificity of T cell subsets in the mouse. Adv Immunol. 1987;41:39–133. doi: 10.1016/s0065-2776(08)60030-9. [DOI] [PubMed] [Google Scholar]

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