Open AccessA distinct cytoplasmic domain of CD2 regulates ligand avidity and T-cell responsiveness to antigen.
Author(s) -
William C. Hahn,
Yvonne Rosenstein,
Vı́ctor Calvo,
Steven J. Burakoff,
Barbara E. Bierer
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.15.7179
Subject(s) - avidity , microbiology and biotechnology , antigen , biology , t cell , cytoplasm , signal transduction , t cell receptor , immunology , immune system
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.