To address whether expression of the relevant MHC molecules on thymic epithelial cells (TEC) is sufficient for positive selection, the fate of CD4+ T cells directed by the DRαE(β)b molecule was compared between two lines of HLA-DRA transgenic mice, DRα-24 expressing DRαE(β)b on TEC and hematopoietic cells, and DRα-30 expressing the molecule on TEC but not on other cell lineages. CD4+ T cells were selected to mature on DRαE(β)b molecules in both lines deficient for the endogenous MHC class I and class II molecules, whereas CD4+ T cell differentiation in DRα-30, as compared with that in DRα-24, was severely impaired when these mice were crossed with mice transgenic for the DRαE(β)b-restricted αβ TCR. In contrast, CD4+ T cells expressing the same TCRαβ as the transgenes were selected to mature in DRα-30 crossed with the single TCRβ transgenic mice. Taken together, these results indicate that the restricted expression of DRαE(β)b on TEC is sufficient for positive selection in the TCRβ and non-TCR transgenic mice, but the expression on both TEC and hematopoietic cells is required for that in the TCRαβ transgenic mice. In the light of the difference in the developmental stage at which αβ TCR are expressed between TCRαβ and TCRβ transgenic mice, the interaction of the TCRαβ with DRαE(β)b molecules expressed on hematopoietic cells required for positive selection in TCRαβ transgenic mice could be mapped to the early stage of T cell differentiation and might mimic 'undefined' early signaling of thymocytes in physiological T cell differentiation.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy