Selecting T cell receptors with high affinity for self-MHC by decreasing the contribution of CD8

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Science  30 Oct 1992:
Vol. 258, Issue 5083, pp. 815-818
DOI: 10.1126/science.1439792


Selective events during T cell repertoire development in the thymus include both the positive selection of cells whose receptors recognize self-major histocompatibility complex (MHC) molecules and negative selection (tolerance) of cells whose interaction with self-MHC is of high affinity. The affinity of T cell interactions with class I MHC molecules includes contributions by both the T cell receptor and the CD8 coreceptor. Therefore, by decreasing the affinity of the interaction with CD8, T cells whose receptors have relatively high affinities for self-MHC may survive negative selection. Such T cells were generated and those T cells reactive with self-MHC plus antigen also displayed low affinity for self.

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