CLONING OF BY55, A NOVEL IG SUPERFAMILY MEMBER EXPRESSED ON NK CELLS,CTL, AND INTESTINAL INTRAEPITHELIAL LYMPHOCYTES

Expression of the BY55 protein has been shown to be tightly associated with NK and CD8(+) T lymphocytes with cytolytic effector activity. To determine the function of this protein, we molecularly cloned BY55 cD NA. The cDNA sequence predicts a cysteine-rich, glycosylphosphatidylin ositol-anchored protein of 181 amino acids with a single Ig-like domai n weakly homologous to killer inhibitory receptors, Reduction and carb oxyamidomethylation of immunoprecipitated BY55 gave a band of 27 kDa, whereas reduction alone led to an 80-kDa species, suggesting that BY55 is a tightly disulfide-linked multimer, RNA blot analysis revealed BY 55 mRNAs of 1.5 and 1.6 kb whose expression was highly restricted to N K and T cells. BY55 was expressed on the CD56(dim), CD16(+) subset of NK cells, which have high cytolytic activity, but was not expressed an d was not induced on the CD56(bright), CD16(-) subset of NK cells, a s ubset with high proliferative, but low cytolytic, capacity, In human t issues, BY55 mRNA was expressed only in spleen, PBL, and small intesti ne tin gut lymphocytes), BY55 was expressed on all intestinal Intraepi thelial lymphocytes, which were predominantly CD3(+)TCR (+)CD11b(+)CD2 8(-)CD45RO(+)CD56(-)CD101(+)CD103(+) (alpha(E)beta(7) integrin). In ad dition, BY55 was expressed on most CD8(+)CD28(-) peripheral blood T ce lls. These phenotypic relationships suggest that CD8(+)CD28(+) precurs or CTL may terminally differentiate into CD8(+)CD28(-)BY55(+) effector CTL and that some of the peripheral blood CD8(+)CD28(-) subset may re present recirculation from mucosal epithelial immune sites.