The capacity of T cells to bind peptide/MHC ligands changes with T cell development and differentiation. Here we study changes in peptide/MHC multimer binding following T cell activation. Surprisingly, T cell activation caused a marked reduction in specific peptide/MHC Class I multimer binding, which was distinct from transient TCR down-regulation, and was especially dramatic for engagement with low-affinity peptide/MHC ligands. Direct CD8-Class I interactions were also profoundly and rapidly impaired following T cell stimulation, even though surface CD8α and CD8β levels were unchanged after activation, suggesting that decreased CD8 co-receptor binding contributes to this effect. Finally, we show that enzymatic desialylation restores much of the multimer binding on activated T cells, suggesting that altered glycosylation may inhibit TCR/CD8 binding to peptide/MHC ligands. These radical changes in activated T cells's; ability to perceive peptide/MHC ligands may contribute to selective outgrowth of clones with high affinity for the stimulatory ligand.
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We are grateful to Don Drake and Tom Braciale for communication of data ahead of publication and numerous helpful discussions, Matt Mescher and members of the Jameson/Hogquist laboratories for their valuable input and Larry Pease (Mayo Clinic, Rochester, MN, USA) for a timely gift of 2C mice. This work was supported by National Institutes of Health grant AI52163 (to S.C.J.) and pre-doctoral training grant awards T32 AI007313 (to both C.K. and M.A.D.).