MHC polymorphism can enrich the T cell repertoire of the species by shiftsin intrathymic selection

The murine class I molecule H-2K(b) and its natural gene conversion variant , H-2K(bm8), which differs from H-2K(b) solely at 4 aa at the bottom of the peptide-binding B pocket, are expressed in coisogenic mouse strains C57BL/ 6 (B6) and B6.C-H-2(bm8) (bm8). These two strains provide an excellent oppo rtunity to study the effects of Mhc class I polymorphism on the T cell repe rtoire. We recently discovered a gain in the antiviral CTL repertoire in bm 8 mice as a consequence of the emergence of the Mhc class I allele H-2(bm8) . In this report we sought to determine the mechanism behind the generation of this increased CTL diversity. Our results demonstrate that repertoire d iversification occurred by a gain in intrathymic positive selection. As pre viously shown, the emergence of the same Mhc allele also caused a loss in p ositive selection of T cell repertoire specific for another Ag, OVA-8, This indicates that a reciprocal loss-and-gain pattern of intrathymic selection exists between H-2Kb and H-2K(bm8). Therefore, in the thymus of an individ ual, a new Mhc allele can select new T cell specificities, while abandoning some T cell specificities selected by the wild type allele, A byproduct of this repertoire shift is a net gain of T cell repertoire of the species, w hich is likely to improve its survival fitness.