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-Chain Connecting Peptide Motif in Mediating TCR-CD8 Cooperation

* Laboratory of Transplantation Immunology and Nephrology, University Hospital, Basel, Switzerland; and
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
To generate peripheral T cells that are both self-MHC restricted
and self-MHC tolerant, thymocytes are subjected to positive and
negative selection. How the TCR discriminates between positive and
negative selection ligands is not well understood, although there is
substantial evidence that the CD4 and CD8 coreceptors play an important
role in this cell fate decision. We have previously identified an
evolutionarily conserved motif in the TCR, the
-chain connecting
peptide motif (
-CPM), which allows the TCR to deliver positive
selection signals. Thymocytes expressing
-CPM-deficient receptors do
not undergo positive selection, whereas their negative selection is not
impaired. In this work we studied the ligand binding and receptor
function of
-CPM-deficient TCRs by generating T cell hybridomas
expressing wild-type or
-CPM-deficient forms of the T1 TCR. This
Kd-restricted TCR is specific for a photoreactive
derivative of the Plasmodium berghei
circumsporozoite peptide252260 IASA-YIPSAEK(ABA)I and is
therefore amenable to TCR photoaffinity labeling. The experiments
presented in this work show that
-CPM-deficient TCRs fail to
cooperate with CD8 to enhance ligand binding and functional
responses.
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