Interplay between TCR affinity and necessity of coreceptor ligation: high-affinity peptide-MHC/TCR interaction overcomes lack of CD8 engagement

SE Kerry, J Buslepp, LA Cramer, R Maile… - The Journal of …, 2003 - journals.aai.org
SE Kerry, J Buslepp, LA Cramer, R Maile, LL Hensley, AI Nielsen, P Kavathas, BJ Vilen…
The Journal of Immunology, 2003journals.aai.org
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 …
Abstract
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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