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* Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN 55905;
Inmunología, Departamento de Microbiología I, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain; and
Laboratory of Transplantation Immunology and Nephrology, Department of Research, University Hospital-Basel, Basel, Switzerland
TCR engagement by peptide-MHC class I (pMHC) ligands induces a conformational change (
c) in CD3 (CD3c) that contributes to T cell signaling. We found that when this interaction took place between primary T lineage cells and APCs, the CD8 coreceptor was required to generate CD3c. Interestingly, neither enhancement of Ag binding strength nor Src kinase signaling explained this coreceptor activity. Furthermore, Ag-induced CD3c was developmentally attenuated by the increase in sialylation that accompanies T cell maturation and limits CD8 activity. Thus, both weak and strong ligands induced CD3c in preselection thymocytes, but only strong ligands were effective in mature T cells. We propose that CD8 participation in the TCR/pMHC interaction can physically regulate CD3c induction by "translating" productive Ag encounter from the TCR to the CD3 complex. This suggests one mechanism by which the developmentally regulated variation in CD8 sialylation may contribute to the developmental tuning of T cell sensitivity.
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1 This work was supported by Dirección General de Universidades e Investigación and Universidad Complutense de Madrid (UCM) program (reference no. 920631), by Ramón y Cajal program (UCM), and by Grant PI060057 from the Instituto de Salud Carlos III. This work is also supported with start-up funds from the Mayo Foundation (to D.G.), the Ruth L. Kirschstein National Research Service Award from the National Cancer Institute, National Institutes of Health, and start-up funds from the Mayo Foundation (to A.G.S.), and by the Cancer Research Foundation (to M.A.D.), EURAPS Novartis, the Swiss National Science Foundation, and Hoffman-LaRoche, Ltd. (to E.P.).
2 Address correspondence and reprint requests to Dr. Ed Palmer, Laboratory of Transplantation Immunology and Nephrology, Department of Research, University Hospital-Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland. E-mail address: ed.palmer{at}unibas.ch or Dr. Diana Gil, Department of Immunology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail address: gilpages.diana{at}mayo.edu
3 Abbreviations used in this paper: pMHC, peptide-MHC class I; CD3-PD, CD3 pull-down; CD3c, conformational change in CD3; DP, double positive; MFI, mean fluorescence intensity; β2m, β2-microglobulin; WT, wild type.
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