CD8 serves both as an adhesion molecule for class I MHC molecules and as a coreceptor with the TCR for T cell activation. Here we study the developmental regulation of CD8-mediated binding to noncognate peptide/MHC ligands (i.e., those not bound by the TCR). We show that CD8's ability to bind soluble class I MHC tetramers and to mediate T cell adhesion under shear flow conditions diminishes as double-positive thymocytes mature into CD8+ T cells. Furthermore, we provide evidence that this decreased CD8 binding results from increased T cell sialylation upon T cell maturation. These data suggest that CD8's ability to interact with class I MHC is not fixed and is developmentally regulated through the T cell's glycosylation state.
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We thank Royce Robinson-Lawler and Bruce Walcheck for help in establishing the adhesion assays, and Matt Mescher and members of the Jameson and Hogquist labs for helpful discussions. We also wish to thank Ellis Reinherz and Jamey Marth for communicating their findings ahead of publication. This work was supported in part by the following grants from the National Institutes of Health: R01 AI38903 (S.C.J.) and R01 CA48115 (P.K.). M.A.D. was supported by an NIH Immunology Training Grant (T32 AI07313).