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Interplay between TCR Affinity and Necessity of Coreceptor Ligation: High-Affinity Peptide-MHC/TCR Interaction Overcomes Lack of CD8 Engagement ¹

Samantha E. Kerry^*, Jennifer Buslepp^*, Lorraine A. Cramer^*, Robert Maile^*, Lucinda L. Hensley^*, Alma I. Nielsen^*, Paula Kavathas, Barbara J. Vilen^*, Edward J. Collins^*, and Jeffrey A. Frelinger^2,*

Departments of ^* Microbiology and Immunology and Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599; and Department of Laboratory Medicine, Yale University, New Haven, CT 06520

CD8 engagement is believed to be a critical event in the activation of naive T cells. In this communication, we address the effects of peptide-MHC (pMHC)/TCR affinity on the necessity of CD8 engagement in T cell activation of primary naive cells. Using two peptides with different measured avidities for the same pMHC-TCR complex, we compared biochemical affinity of pMHC/TCR and the cell surface binding avidity of pMHC/TCR with and without CD8 engagement. We compared early signaling events and later functional activity of naive T cells in the same manner. Although early signaling events are altered, we find that high-affinity pMHC/TCR interactions can overcome the need for CD8 engagement for proliferation and CTL function. An integrated signal over time allows T cell activation with a high-affinity ligand in the absence of CD8 engagement.

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