Major histocompatibility complex class I‐specific receptors on human natural killer and T lymphocytes

Abstract

Summary: Human NK cells express several specialized inhibitory receptors that recognize major histocompatibility complex (MHC) class I molecules expressed on normal cells. The lack of expression of one or more HLA CLASS I alleles leads to NK‐mediated target cell lysis. Receptors specific for groups of HLA‐C (p58), HLA‐B (p70) and HLA‐A (p140) alleles belong to the Ig superfamily with two or three Ig‐like domains in their extracellular portion, and a long cytoplasmic tail containing ITIM motifs and associated with a non‐polar transmembrane portion. In contrast, the CD94/NKG2‐A receptor complex is composed of type II proteins with a C‐type lectin domain which displays a more broad specificity for different class I alleles. Recently, activatory forms of the HLA‐C‐specific receptors have been identified in some donors. They are virtually identical to the inhibitory forms in their extracellular portions, but display a short cytoplasmic tail lacking ITIM motifs associated with a Lys‐containing transmembrane portion (p50). A subset of activated T‐lymphocytes. primarily CD8+ and oligoclonal or monoclonal in nature, express NK‐type class I‐specific receptors. These receptors exert an inhibitory activity on T‐cell receptor‐mediated functions and may provide an important mechanism of down‐regulation of T‐cell responses.