A distinct cytoplasmic domain of CD2 regulates ligand avidity and T-cell responsiveness to antigen.
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.
Hahn
W C
WC
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
Rosenstein
Y
Y
Calvo
V
V
Burakoff
S J
SJ
Bierer
B E
BE
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001224:Aspartic Acid; D018801:CD2 Antigens; D017252:CD3 Complex; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003593:Cytoplasm / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D001224:Aspartic Acid; D013755:Tetradecanoylphorbol Acetate