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¹ Lymphocyte Development Group, MRC Clinical Sciences Centre, ICSM Hammersmith Hospital, London W12 0NN, UK
² Division of Molecular Immunology, National Institute for Medical Research, London NW7 1AA, UK
³ Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK

Address correspondence to Matthias Merkenschlager, Lymphocyte Development Group, MRC Clinical Sciences Centre, ICSM Hammersmith Hospital, Du Cane Rd., London W12 0NN, UK. Phone: 44-20-8383-823-9/-6; Fax: 44-20-8383-8338; E-mail: matthias.merkenschlager{at}csc.mrc.ac.uk

T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of T cells in the thymus as well as their homeostasis in peripheral lymphoid organs. Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56^lck. Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca²+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen. Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

Key Words: T cell receptor repertoire • T cell responsiveness • CD5 • MHC contact • p56^lck

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