Differential MHC expression requirements for positive selection of separate TCR Vb families

Positive selection has been proposed to be involved in protection from diab etes. We examined positive selection by fluorescence-activated cell sorter analyses in thymocytes of protected and susceptible E-transgenic and non-tr ansgenic NOD mice. Three Vb families showed positive selection in E-transge nic mice. Vb6(+) CD4(+) and Vb10(+) CD4(+) thymocytes were found at higher frequencies in both protected NOD-Ea and susceptible NOD-DY mice. The incre ased frequencies of Vb13(+) CD8(+) thymocytes were found in protected NOD-E a 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 n on-transgenic NOD mice, where we could examine the contribution of E-expres sing bone-marrow-derived cells in positive selection. We find that NOD-Ea - -> NOD-Ea chimeras have an increased positive selection of Vb13(+) CD8(+) c ells and that positive selection is more efficient when both thymic epithel ium and bone-marrow-derived cells express the E molecule. This was also see n for Vb6(+) CD4(+) cells. However, for Vb6, bone-marrow-derived cells alon e were also capable of positive selection. Positive selection of Vb10(+) CD 4(+) 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, althoug h positive selection also occurs with E-positive epithelium only. For Vb6() CD4(+) cells, the dominating selecting cells are bone-marrow-derived cell s, and Vb10(+) CD4(+) cells seem to be selected exclusively by the thymic e pithelium. Thus, the conditions for positive selection seem to vary conside rably between different Vb families.