MHC polymorphism can enrich the T cell repertoire of the species by shifts in intrathymic selection Journal Article
| Authors: | Dyall, R.; Messaoudi, I.; Janetzki, S.; Nikolić-Žugić, J. |
| Article Title: | MHC polymorphism can enrich the T cell repertoire of the species by shifts in intrathymic selection |
| Abstract: | 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 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- 2K(bm8). 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-2K(b) and H-2K(bm8). 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. |
| Keywords: | controlled study; nonhuman; t lymphocyte; animal cell; mouse; animals; mice; allele; cell survival; animal experiment; animal model; strain difference; mice, inbred c57bl; species specificity; thymus; thymus gland; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; simplexvirus; t-lymphocyte subsets; major histocompatibility complex; polymorphism, genetic; receptors, antigen, t-cell, alpha-beta; genetic polymorphism; genetic selection; viral proteins; major histocompatibility antigen class 1; h-2 antigens; priority journal; article |
| Journal Title: | Journal of Immunology |
| Volume: | 164 |
| Issue: | 4 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2000-02-15 |
| Start Page: | 1695 |
| End Page: | 1698 |
| Language: | English |
| PUBMED: | 10657612 |
| PROVIDER: | scopus |
| DOI: | 10.4049/jimmunol.164.4.1695 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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