Abstract
Abstract CD244 (2B4) is a member of the signaling lymphocyte activation molecule (SLAM) family of receptors and is expressed on all murine NK cells and a subset of CD8+ T cells. The SLAM family of receptors exists as one of two stable haplotypes (b and z haplotype) in common laboratory strains of mice. The b haplotype is associated with C57-derived mouse strains while the z haplotype is found in most other inbred strains. Previous studies have shown that CD244 exhibits inhibitory function in NK cells from C57BL/6 (B6) mice. Here we employ a congenic mouse strain (B6.Sle1b) that differs from the parental solely at a region of chromosome 1 containing the SLAM family of genes to characterize the function of the z haplotype of CD244. We show that the more common haplotype of CD244 exhibits activating function in an SH2D1a dependent manner as evidenced by enhanced lytic activity towards targets expressing the ligand for CD244, CD48. The activating function of the z version of CD244 is due to polymorphic differences that appear to be clustered in the ligand-binding region of the receptor. In addition, we observed differential baseline phosphorylation and adaptor association for each of the CD244 haplotypes in cultured NK cells accounting for their functional differences.
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