Differential MHC expression requirements for positive selection of separate TCR Vb families.
Positive selection has been proposed to be involved in protection from diabetes. We examined positive selection by fluorescence-activated cell sorter analyses in thymocytes of protected and susceptible E-transgenic and non-transgenic NOD mice. Three Vb families showed positive selection in E-transgenic mice. Vb6(+)CD4(+) and Vb10(+)CD4(+) thymocytes were found at higher frequencies in both protected NOD-Ea and susceptible NOD-DY mice. The increased frequencies of Vb13(+)CD8(+) thymocytes were found in protected NOD-Ea mice only, and not in susceptible NOD-DY transgenic mice. These three Vb families were further examined in bone-marrow chimeras between NOD-Ea and non-transgenic NOD mice, where we could examine the contribution of E-expressing bone-marrow-derived cells in positive selection. We find that NOD-Ea-->NOD-Ea chimeras have an increased positive selection of Vb13(+)CD8(+) cells and that positive selection is more efficient when both thymic epithelium and bone-marrow-derived cells express the E molecule. This was also seen for Vb6(+)CD4(+) cells. However, for Vb6, bone-marrow-derived cells alone were also capable of positive selection. Positive selection of Vb10(+)CD4(+) cells was restricted to E-expressing thymic epithelium only. For Vb13(+)CD8(+ )cells, we found that positive selection is most efficient with E-expression on both thymic epithelium and bone-marrow-derived cells, although positive selection also occurs with E-positive epithelium only. For Vb6(+) CD4(+) cells, the dominating selecting cells are bone-marrow-derived cells, and Vb10(+)CD4(+ )cells seem to be selected exclusively by the thymic epithelium. Thus, the conditions for positive selection seem to vary considerably between different Vb families.
Brenden
N
N
Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden.
Böhme
J
J
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D017637:Clonal Deletion; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta