Cloning of Immunoglobulin-Superfamily Members Associated with HLA-C and HLA-B Recognition by Human Natural Killer Cells

TLDR

NK cell cytotoxicity is suppressed by MHC class I molecules on target cells, a process thought to involve NK receptors with distinct MHC specificities. The authors identified four NKAT cDNAs encoding transmembrane proteins with two or three Ig‑superfamily domains and a cytoplasmic antigen‑receptor activation motif. NKAT distribution is clonotypic and aligns with inhibition by specific class I alleles, indicating these cDNAs encode class I‑recognizing receptors on NK cells.

Abstract

Cytotoxicity by natural killer (NK) cells is inhibited by major histocompatibility complex (MHC) class I molecules on target cells. This inhibition may be mediated by NK receptors with different MHC specificities. A family of four NK-specific complementary DNAs (cDNAs), designated NKATs (NK-associated transcripts), was identified that encoded related transmembrane proteins, characterized by an extracellular region with two or three immunoglobulin-superfamily domains and by a cytoplasmic domain with an unusual antigen receptor activation motif (ARAM). The distribution of these cDNAs was clonotypic and correlated with NK cell inhibition by particular class I alleles. Thus, NKAT cDNAs may encode receptors for class I molecules on NK cells.