T-cell receptors generated via mutations are specific for various major histocompatibility antigens.
T cells that are positively selected in ontogeny could give rise to somatic mutants with new reactivities. Hence, somatic generation of diversity via mutations could be a source of expansion for the T-cell repertoire. To test this idea we searched among the progenies of an Ed alpha Ed beta-specific T-cell hybridoma for mutant clones capable of recognizing MHC antigens of a different haplotype. We isolated clones in which the original reactivity to Ed alpha Ed beta diminished substantially or disappeared, while new specificities (for Ab alpha Ab beta and/or Ak alpha Ak beta) were detected. In both alpha and beta subunits of receptors isolated from these T-hybrid clones, structural differences were observed using IEF, NEPHGE, and two-dimensional tryptic peptide maps. Thus changes in MHC specificity occurred via mutations affecting the T-cell receptor structure.
D000818:Animals; D000911:Antibodies, Monoclonal; D006183:H-2 Antigens / Q000235:genetics; D006649:Histocompatibility Antigens / Q000235:genetics*; D006825:Hybridomas / Q000276:immunology; D007376:Interleukin-2 / Q000032:analysis; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010446:Peptide Fragments / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D013945:Thymoma / Q000276:immunology; D013953:Thymus Neoplasms / Q000276:immunology
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell