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.