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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Aug 1;89(15):7179–7183. doi: 10.1073/pnas.89.15.7179

A distinct cytoplasmic domain of CD2 regulates ligand avidity and T-cell responsiveness to antigen.

W C Hahn 1, Y Rosenstein 1, V Calvo 1, S J Burakoff 1, B E Bierer 1
PMCID: PMC49669  PMID: 1353888

Abstract

The T-cell glycoprotein CD2 not only contributes to intercellular adhesion but also plays a direct role in T-cell activation. Here we demonstrate that the interaction of CD2 with its ligand lymphocyte function-associated antigen 3 (CD58) is regulated by T-cell receptor-CD3 signaling. T-cell receptor-CD3 crosslinking by specific antigen or monoclonal antibodies rapidly increases the avidity with which cell-surface CD2 binds immunoaffinity-purified CD58. Mutational analysis of the CD2 cytoplasmic domain demonstrates that the carboxyl-terminal asparagine is essential for T-cell receptor-induced changes in CD2 avidity but is not essential for CD2-mediated signaling, establishing that the cytoplasmic portion of CD2 consists of distinct functional domains. Furthermore, cell lines expressing CD2 molecules incapable of avidity regulation exhibit a marked deficiency in an antigen-specific response. Thus, the regulation of CD2 adhesiveness has a profound effect on the ability of CD2 to enhance antigen responsiveness. These observations demonstrate that adhesion strengthening resulting from increased CD2 avidity contributes directly to T-cell responsiveness independently of CD2-mediated signal transduction.

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