Recombinant Human CRTAM Fc Chimera Protein, CF

CRTAM (Class I-restricted T cell-associated molecule) is a nectin family member of the immunoglobulin superfamily that is expressed by activated CD8⁺ and NK T cells (1 - 4). NK activation receptor engagement, but not cytokines, also induce NK CRTAM expression (4, 5). CRTAM is found in spleen, thymus, small intestine, peripheral blood, and surprisingly, in brain where it is highly expressed by Purkinje cells of the cerebellum (1, 2). Human CRTAM is a 393 amino acid (aa), 80 kDa type I transmembrane glycoprotein with a 17 aa signal sequence, a 269 aa extracellular domain (ECD), a 21 aa transmembrane segment and an 84 aa cytoplasmic domain. The ECD has one V-type and one C1-type Ig-like domain, while the cytoplasmic region shows a potential class I PDZ domain (1 - 5). Human CRTAM ECD shows 70%, 43% and 63% aa identity with mouse, rat and canine CRTAM ECD, respectively, but 73 - 78% aa identity within the Ig-like domains. The V-type Ig-like domain mediates interaction with the corresponding domain on another nectin family member, IGSF4 (also called TSLC-1, Necl-2, Syncam or SgIGSF) (4, 5). CRTAM is a homodimer on the cell surface but does not show homotypic binding in trans (3 - 5). The high affinity of CRTAM/IGSF4 adhesion allows CRTAM to disrupt IGSF4 homotypic interactions (3 - 5). IGSF4 and T cell receptor co-engagement of CRTAM-expressing CD8⁺ cells induces increased IFN-gamma or IL-22 production (3, 4). A role in cancer surveillance through NK cell-mediated rejection of IGSF4-expressing tumors has been proposed (3 - 5). IGSF4 is expressed broadly, including on epithelia, neurons, a subset of tonsillar B cells (4, 5), and a rare splenic T zone-restricted BCDA3+ dendritic cell population which interacts with CRTAM (3).