T cell adhesion, avidity regulation and signaling: a molecular analysis of CD2.
While the T cell receptor (TcR) recognizes cell bound, peptide antigens embedded within major histocompatibility complex (MHC) proteins, this interaction is not sufficient for T cell activation and function. A number of other cell surface molecules, termed co-receptors or accessory molecules, cooperate with the TcR by participating in T cell adhesion to antigen presenting cells (APC) and/or by contributing to T cell signaling. In addition, recent evidence suggests that T cell activation can, in turn, increase the avidity of several of these co-receptors for their ligands. One such co-receptor molecule is CD2, a T cell glycoprotein that not only participates in T cell activation but also provides the T cell with a major adhesion pathway whose avidity is regulated by TcR triggering. Using both cellular and molecular biological approaches, we have mapped the portions of CD2 involved in CD2-dependent signaling and in the regulation of avidity for its ligand CD58 (lymphocyte function associated antigen-3, LFA-3) to structurally distinct portions of the cytoplasmic domain. This delineation of function has allowed us to analyze the contribution of co-receptor basal adhesion, signaling, and avidity regulation in antigen-dependent T cell interactions. The signal transduction pathways recruited for the regulation of CD2 avidity for its ligand differ from those used by other co-receptors such as LFA-1 and CD8 for their respective ligands. Taken together, the multiplicity of co-receptors, their interplay, and their differential regulation contribute to the control and the sensitivity of antigen-dependent immune responses.
Bierer
B E
BE
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
Hahn
W C
WC
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry / Q000502:physiology*; D018801:CD2 Antigens; D018968:CD58 Antigens; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011971:Receptors, Immunologic