Mutations in the major histocompatibility complex class I antigen‐presenting groove affect both negative and positive selection of T cells

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Abstract
In several transgenic mouse models T cell development was shown to be controlled by the binding of the α/β T cell receptor (TcR) to ligands in the thymus. In transgenic mice expressing a male-specific TcR α/β, the presence of the restricting Db major histocompatibility complex (MHC) molecule plus the male specific peptide deleted thymocytes at an early stage of development. On the other hand, maturation of T cells required an interaction of the TcR with the thymic Db MHC molecules in the absence of specific peptides. This could imply that negative and positive selection of this receptor are affected differently by mutations in the HY peptide-binding groove of the Db MHC molecule. Such mutants have been isolated and were shown to affect the response to HY antigen in that both the bm14 (residue Glu70 → Asp) and the bm13 (residue Leu114 → Glu, Phe116 → Tyr and Glu119 → Asp) strains do not normally mount cytotoxic responses to male cells. Here we show that these mutations affect antigenicity of male cells, as well as negative and positive selection of T cells in TcR α/β transgenic mice.

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