THE HUMAN-LEUKOCYTE ANTIGEN (HLA)-C-SPECIFIC ACTIVATORY OR INHIBITORYNATURAL-KILLER-CELL RECEPTORS DISPLAY HIGHLY HOMOLOGOUS EXTRACELLULARDOMAINS BUT DIFFER IN THEIR TRANSMEMBRANE AND INTRACYTOPLASMIC PORTIONS

Natural killer cells express clonally distributed receptors specific f or major histocompatibility complex class I molecules. The human leuko cyte antigen (HLA)-C-specific receptors have been molecularly identifi ed and cloned. They exist not only as inhibitory (p58) but also as act ivatory (p50) receptors. Here we show that p50 and p58 are highly homo logous in their extracellular regions formed by true Ig-like domains. In contrast, major differences exist in their transmembrane and cytopl asmic portions. Whereas p58 displays a 76-84-amino acid cytoplasmic ta il containing an unusual antigen receptor activation motif, p50 is cha racterized by a shorter 39-amino acid tail. In addition, whereas p58 h as a nonpolar transmembrane portion, p50 contains the charged amino ac id Lys. These data strongly suggest that receptors with identical HLA- C allele specificity can mediate functions of opposite sign owing to t heir different transmembrane/cytoplasmic portions.