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J Immunol. 2010 Oct 15;185(8):4625-32. doi: 10.4049/jimmunol.1001480. Epub 2010 Sep 15.

CD8 controls T cell cross-reactivity.

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Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, UK.


Estimates of human αβ TCR diversity suggest that there are <10(8) different Ag receptors in the naive T cell pool, a number that is dwarfed by the potential number of different antigenic peptide-MHC (pMHC) molecules that could be encountered. Consequently, an extremely high degree of cross-reactivity is essential for effective T cell immunity. Ag recognition by T cells is unique in that it involves a coreceptor that binds at a site distinct from the TCR to facilitate productive engagement of the pMHC. In this study, we show that the CD8 coreceptor controls T cell cross-reactivity for pMHCI Ags, thereby ensuring that the peripheral T cell repertoire is optimally poised to negotiate the competing demands of responsiveness in the face of danger and quiescence in the presence of self.

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