MHC polymorphism can enrich the T cell repertoire of the species by shifts in intrathymic selection.
The murine class I molecule H-2Kb and its natural gene conversion variant, H-2Kbm8, which differs from H-2Kb 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-2bm8 (bm8). These two strains provide an excellent opportunity to study the effects of Mhc class I polymorphism on the T cell repertoire. We recently discovered a gain in the antiviral CTL repertoire in bm8 mice as a consequence of the emergence of the Mhc class I allele H-2Kbm8. In this report we sought to determine the mechanism behind the generation of this increased CTL diversity. Our results demonstrate that repertoire diversification occurred by a gain in intrathymic positive selection. As previously shown, the emergence of the same Mhc allele also caused a loss in positive 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-2Kbm8. Therefore, in the thymus of an individual, 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, which is likely to improve its survival fitness.
Dyall
R
R
Laboratory of T Cell Development, Swim Across America Laboratory, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Messaoudi
I
I
Janetzki
S
S
Nikolic-Zugić
J
J
D000818:Animals; D004268:DNA-Binding Proteins; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D011110:Polymorphism, Genetic / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D018139:Simplexvirus / Q000276:immunology; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014764:Viral Proteins / Q000276:immunology
D004268:DNA-Binding Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C045462:ICP8 protein, Simplexvirus; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014764:Viral Proteins