Weak positive selection of transgenic T cell receptor-bearing thymocytes: importance of major histocompatibility complex class 11, T cell receptor and CD4 surface molecule densities*
We have produced up Tcell receptor (TcR)-transgenic mice and studied MHC-dependent positive selection of T cells bearing this receptor. The u and fl transgenes were isolated from an I-Ed-restricted, CD4+ BALBk (H-2d/d) T cell clone specific for a peptide consisting of the 91-101 residues of the hz immunoglobulin light chain of MOPC315. Mice which carry the transgenes on a BALBk background, but with H-2d/d, H-2b/d or H-2b/b major histocompatibility complex (MHC) haplotypes, were investigated for TcR expression in thymocytes and peripheral T cells. The thymocytes expressing the transgene-encoded ap receptor are weakly positively selected when compared with previous findings in other TcR-transgenic mice models. Thus, up thymocytes vary in their efficacy of being positively selected by their restriction element. Furthermore, the density of TcR and CD4 on thymocytes, as well as the density of I-Ed molecules on thymic epithelial cells, appear critical for the extent of positive selection. A possible explanation is that the transgenic TcR has a marginal affinity for self-MHC molecules on thymic epithelium, and that this may be compensated for by an increase in the number of CD4/TcR/MHC ternary complexes forming between the maturing thymocyte and the cortical epithelial cells.