T cell receptor binding and unrestricted reactivity to GLT in somatic variants of an I-Ek specific T cell hybrid.
T helper cell responsiveness to some synthetic polypeptides is controlled by Ir genes. It has been suggested that the inability of class II complexes to associate with conventional soluble antigens, on the surface of antigen presenting cells, can result in a characteristic pattern of antigen-specific T cell unresponsiveness, mapping to the I region of the MHC. Alternatively, during the establishment of self-tolerance, a hiatus could be generated in the T cell repertoire, when an epitope exhibited by a conventional antigen topochemically resembled (per se or in association with a self MHC epitope) a potentially immunogenic self antigenic determinant. The synthetic polypeptide GLT offers an interesting possibility for investigating the connection between tolerance to self-MHC antigens and Ir gene controlled unresponsiveness. It has been shown that mice which do not express I-Ek possess significant numbers of T cells which aberrantly recognize GLT in the context of various allogeneic class II MHC molecules. Moreover, if T cell populations obtained from such mice are depleted of alloreactivity to I-Ek in vitro, it results in the deletion of T cell clones specific for GLT presented by several I-A and I-E molecules. These observations are compatible with the hypothesis that GLT alone can mimic an I-Ek epitope, thus being able to interact directly with some of the T-cell receptors specific for I-Ek. Experiments presented in this communication indicate that GLT specifically inhibits the proliferation in vitro of a fraction of the MLR blasts generated against I-Ek. In addition, we characterize a T cell hybrid clone specific for I-Ek which can be functionally modulated by GLT.(ABSTRACT TRUNCATED AT 250 WORDS)
MacNeil
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IA
Department of Medicine, National Jewish Hospital, Denver, CO 80206.
Sim
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GK
Augustin
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007108:Immune Tolerance; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D011108:Polymers; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007519:Isoantigens; D010455:Peptides; D011108:Polymers; D011948:Receptors, Antigen, T-Cell; C022272:glutamic acid-lysine-tyrosine terpolymer