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T cell receptor engagement by peptide-MHC ligands induces a conformational change in the CD3 complex of thymocytes

Diana Gil1, Adam G Schrum, Balbino Alarcón

  • 1Department of Research, Laboratory of Transplantation Immunology and Nephrology, University Hospital-Basel, CH-4031 Basel, Switzerland.

The Journal of Experimental Medicine
|February 25, 2005
PubMed

The T cell receptor (TCR) can recognize a variety of cognate peptide/major histocompatibility complex (pMHC) ligands and translate their affinity into distinct cellular responses. To achieve this, the nonsignaling alphabeta heterodimer communicates ligand recognition to the CD3 signaling subunits by an unknown mechanism. In thymocytes, we found that both positive- and negative-selecting pMHC ligands expose a cryptic epitope in the CD3 complex upon TCR engagement. This conformational change is induced in vivo and requires the expression of cognate MHC. We conclude that TCR engagement with a cognate pMHC ligand induces a conformational change in the CD3 complex of thymocytes and propose that this marks an initial event during thymic selection that signals the recognition of self-antigen.

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