2B4 (CD244) and CS1: novel members of the CD2 subset of the immunoglobulinsuperfamily molecules expressed on natural killer cells and other leukocytes

2B4 is a member of the CD2 subset of the immunoglobulin superfamily molecul es expressed on natural killer (NK) cells and other leukocytes. It is the h igh affinity ligand for CD48. Engagement of 2B4 on NK-cell surfaces with sp ecific antibodies or CD48 can trigger cell-mediated cytotoxicity, interfero n-gamma secretion, phosphoinositol turnover and NK-cell invasiveness. The f unction of 2B4 in CD8(+) T cells and myeloid cells remains unknown, The cyt oplasmic domain of 2B4 contains unique tyrosine motifs (TxYxxV/I) that asso ciate with src homology 2 domain-containing protein or signaling lymphocyte activation molecule (SLAM)-associated protein, whose mutation is the under lying genetic defect in the X-linked lymphoproliferative disease (XLPD). Im paired signaling via 2B4 and SLAM is implicated in the immunopathogenesis o f XLPD. CS I is a novel member of the CD2 subset that contains two of the u nique tyrosine motifs present in 2B4 and SLAM. Signaling through 2B4, CS I and other members of the CD2 subset may play a major role in the regulation of NK cells and other leukocyte functions.