Mouse xenoantigens contribute to rat T-cell Vbeta repertoire generation in mixed xenogeneic bone marrow chimeras.
We previously demonstrated that rat bone-marrow-derived cells in mixed xenogeneic chimeras (rat + mouse --> mouse) contribute to peripheral selection of mouse T-cell receptor (TCR) variable betas (Vbetas) repertoire. In this study, we analysed rat T cells that developed in the chimeras to assess the contribution of mouse xenoantigens to the development of rat TCR repertoire. The expression of rat Vbetas was analysed using flow cytometry and a reverse transcription-polymerase chain reaction (RT-PCR) method that allows for both semiquantitative analysis of rat Vbeta gene expression and size heterogeneity of the complementarity determining region 3 (CDR3) domain. Three distinct patterns of Vbeta expression were detected. Partial deletion was observed for Vbeta5, 7, 12, 14, 16, 17 and 20 that exhibited reduced levels of peripheral expression by 3.4-, 1.8-, 8.7-, 2.0-, 7.8-, 9.5- and 1.8-fold, respectively, compared with the levels of Vbetas in naYve rats. Higher levels of peripheral expression were detected for three rat Vbeta genes; Vbeta6 (2.2-fold), Vbeta8.2 (3.2-fold), and Vbeta9 (1.7-fold). The relative expression of the other 10 known rat Vbeta families in chimeras was unchanged as compared with that of normal rats. We did not observe detectable changes in the pattern of CDR3 expression in chimeras, suggesting that the mouse xenogeneic environment exerted its influence on the development of rat T cells via the Vbeta-encoded CDR1/2 domains. Our data demonstrate that the rat T-cell repertoire in chimeras is shaped by both contractions as well as expansions of selected Vbetas and suggest that mouse xenoantigens and/or superantigens of endogenous mouse retroviruses may contribute as ligands for these selection processes
Institute for Cellular Therapeutics and Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA.
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Huang
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Ildstad
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Neipp
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Shirwan
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D022801:Complementarity Determining Regions; D006085:Graft Survival / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011916:Rats, Inbred F344; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016038:Skin Transplantation / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology*
D015478:Antigens, Heterophile; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta