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Co-engagement of CD8 with the T cell receptor is required for negative selection

Abstract

ALTHOUGH it is established that the CDS and CD4 co-receptors are involved in T-lymphocyte recognition and activation in the periphery, it is less clear whether these molecules participate in thymic selection events. Analysis of thymic selection in mice transgenic for T cell-receptor genes1–4 or for major histocompatibility complex (MHC) genes5, or mice injected with antibodies against CDS, CD4 or MHC molecules6–8, is consistent with the participation of CDS and CD4 in thymic selection. But antibody-mediated crosslinking of surface receptors in thymic organ cultures9 has indicated that CDS is not involved in thymic deletion. We show here that mice transgenic for a mutant MHC class I molecule that cannot interact with CDS do not delete CDS-dependent T cells reactive with the wild-type molecule. This finding unequivocally establishes that for negative selection in the thymus, CDS must interact with the same MHC class I molecule as the T cell receptor.

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Ingold, A., Landel, C., Knall, C. et al. Co-engagement of CD8 with the T cell receptor is required for negative selection. Nature 352, 721–723 (1991). https://doi.org/10.1038/352721a0

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