The CD2 family represents a subset of the immunoglobulin superfamily of cell surface receptor. It consists of multiple members, including CD2, CD48, CD58, CD84, 2B4, Ly9, CDw150 or SLAM (Signalling lymphocyte activation molecule), NAIL and Ly108, all of which share a similar pattern of Ig-like folds in their extracellular domains. Family members are characterized by a N-terminal variable (V) domain lacking disulfide bonds and a membrane-proximal C2 domain containing two conserved disulfide bonds. An exception is Ly9, in which the V-CD2-like sequences have been duplicated, resulting in an extracellular domain containing four Ig-like folds. Furthermore, the genes encoding CD2 family members are clustered on mouse Chromosome (Chr) 1 and 3 and on two syntenic pericentric loci on human Chr 1, suggesting that they arose through duplication of a common ancestral precursor.
Members of the CD2 receptor family are expressed predominantly on hematopoietic cells, suggesting that they may roles in the immune response. Experiments with knockout mice have revealed a role for CD2 in setting threshold levels of antigen required to stimulate T cells, and a more pronounced role for CD48 in the activation of CD4+ lymphocytes. The only known ligands of CD2-related receptors are other CD2 family members, such that CD2 binds to CD58 and to CD48, SLAM interacts with itself and CD48 interacts with 2B4. Interaction of a receptor/ligand pair may contribute indirectly to signal transduction, through the reorganization of signalling components in the target cell, or by promoting contact between cells. Alternatively, some CD2-like receptors may transduce signals directly. Studies using monoclonal antibodies have implicated CD2 in antigen-independent T cell activation and protection of B cells from apoptosis. Furthermore, several receptors, such as SLAM and 2B4, contain cytoplasmic SH2-binding motifs that associate with the intracellular signalling molecules SHP-2 and SAP in vivo.
Ly108 is most closely related to CD84 and Ly9. The Ly108 genes encodes a protein of 331 amino acids. Expression of Ly108 mRNA appears highly restricted and was detected only in hematopoietic tissues and in cultured mouse B- and T-cell lines.
The cytoplasmic domain of 2B4 can interact with SAP, a signalling adaptor protein that is mutated in the immunodeficiency X-linked lymphoproliferative disease (XLP). The natural ligand of 2B4 has been identified as CD48. The interaction between 2B4 on effector cells and CD48 on target cells induced NK-cell activation, as evidenced by increased cytotoxicity and secretion of IFN-γ.
CD2 family members