Alterations in CD4-binding regions of the MHC class II molecule I-E-k do not impede CD4(+) T cell development

The T cell coreceptors CD4 and CD8 enhance T cell responses to TCR signals by participating in complexes containing TCR, coreceptor, and MHC molecules , These ternary complexes are also hypothesized to play a seminal role duri ng T cell development, although the precise timing, frequency, and conseque nces of TCR-coreceptor-MHC interactions during positive selection and linea ge commitment remain unclear. To address these issues, we designed transgen ic mice expressing mutant I-E-k molecules with reduced CD4-binding capabili ty. These transgenic lines mere crossed to three different lines of I-E-k-s pecific TCR transgenic mice, and the efficiency of production of CD4(+) lin eage cells in the doubly transgenic progeny was assessed. Surprisingly, rep lacing wild-type I-E-k molecules with these mutant molecules did not affect the production or CD4(+)CD8(-) thymocytes or CD4(+) peripheral T cells exp ressing any of the three TCRs examined. These data, when considered togethe r with other experiments addressing the role of coreceptor during developme nt, suggest that not all MHC class II-specific thymocytes require optimal a nd simultaneous TCR-CD4-MHC interactions to mature. Alternatively, it is po ssible that these particular alterations of I-E-k do not disrupt the CD4-MH C interaction adequately, potentially indicating functional differences bet ween I-A and I-E MHC class II molecules.