CD48, also known as BLAST-1, BCM-1, and SLAMF2, is a 65 kDa GPI-linked protein in the CD2 family of immunoglobulin superfamily proteins (1-3). The human CD48 cDNA encodes a 243 amino acid (aa) precursor that includes a 26 aa signal sequence, a 194 aa mature protein containing two Ig-like C2-type domains, and a 23 aa C-terminal propeptide (4). A soluble form of CD48 has been detected in the serum of lymphoid leukemia and arthritis patients (5). Human CD48 shares approximately 50% aa sequence identity with mouse and rat CD48. It shares 20%-26% aa sequence identity with comparable regions of human 2B4, BLAME, CD2F-10, CD84, CD229, CRACC, NTB-A, and SLAM. CD48 is expressed on most lineage-committed hematopoietic cells but not on hematopoietic stem cells or multipotent hematopoietic progenitors (4, 6). Among dendritic cells (DC), CD48 is selectively expressed on circulating myeloid DC and resident bone marrow and thymus DC (7). CD2, 2B4, and heparan sulfate function as CD48 ligands (8-10). CD48 is competent to transduce signals and can also trigger signaling through CD2 or 2B4 (8, 11). CD48-CD2 interactions promote T cell activation and class switching to IgG _2a in B cells (8, 12). High affinity CD48-2B4 interactions can either promote or inhibit NK cell and cytotoxic T cell (CTL) activation (7, 11, 13, 14). CD48-2B4 ligation does not directly trigger CTL activity but enhances signaling from the T cell receptor (13). CD48-2B4 mediated inhibition of NK cell activity is distinct from MHC I-restricted mechanisms (15). CD48 expressed on NK cells is co-activating, whereas CD48 expressed on other cell types inhibits NK cell activation (14). Both CD48 expressing and non-expressing cells can be targets of NK cell or
CTL-mediated lysis (13, 16).