... MHC haplotype a is lethally irradiated and reconstituted with bone marrow of a F1 strain with MHC haplotype a x b, the T-cells which develop exclusively respond to antigens presented by APCs expressing MHC haplotype a. This shows that the T-cell receptor repertoire has been positively selected by cells of the recipient mouse as T cells recognizing MHC b were eliminated during development. In addition to the MHC molecules, self-antigens play an important role in positive selection. This has been shown in knockout mice on a TCR beta-chain transgenic background where the expressed self-Ags were restricted to the invariant CLIP. These mice generate a much more limited repertoire that TCR beta-chain transgenic WT mice. This suggests that positive selection involves combinatorial recognition of MHC + self-peptide, rather than just the MHC alone as suggested by the BM chimera experiments. This is very similar to the situation in negative selection. Recent ...

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