MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-SPECIFIC RECEPTORS ON HUMAN NATURAL-KILLER AND T-LYMPHOCYTES

Human NK cells express several specialized inhibitory receptors that r ecognize major histocompatibility complex (MHC) class I molecules expr essed 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 extr acellular portion, and a long cytoplasmic tail containing ITIM motifs and associated with a non-polar transmembrane portion. In contrast, th e CD94/NKG2-A receptor complex is composed of type II proteins with a C-type lectin domain which displays a more broad specificity for diffe rent class I alleles. Recently, activatory forms of the HLA-C-specific receptors have been identified in some donors. They are virtually ide ntical to the inhibitory forms in their extracellular portions, but di splay a short cytoplasmic tail lacking ITIM motifs associated with a L ys-containing transmembrane portion (p50). A subset of activated T-lym phocytes, primarily CD8+ and oligoclonal or monoclonal in nature, expr ess NK-type class I-specific receptors. These receptors exert an inhib itory activity on T-cell receptor-mediated functions and may provide a n important mechanism of downregulation of T-cell responses.