Analysis of Mlsc genetics. A novel instance of genetic redundancy.
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.
Abe
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R
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
Foo-Phillips
M
M
Hodes
R J
RJ
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D000939:Epitopes; D005796:Genes; D008040:Genetic Linkage; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D008912:Minor Histocompatibility Loci; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000954:Antigens, Surface; D000939:Epitopes; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta