The human leukocyte antigen (HLA)-C-specific "activatory" or "inhibitory" natural killer cell receptors display highly homologous extracellular domains but differ in their transmembrane and intracytoplasmic portions.
Natural killer cells express clonally distributed receptors specific for major histocompatibility complex class I molecules. The human leukocyte antigen (HLA)-C-specific receptors have been molecularly identified and cloned. They exist not only as inhibitory (p58) but also as activatory (p50) receptors. Here we show that p50 and p58 are highly homologous in their extracellular regions formed by two Ig-like domains. In contrast, major differences exist in their transmembrane and cytoplasmic portions. Whereas p 58 displays a 76-84-amino acid cytoplasmic tail containing an unusual antigen receptor activation motif, p50 is characterized by a shorter 39-amino acid tail. In addition, whereas p58 has a nonpolar transmembrane portion, p50 contains the charged amino acid Lys. These data strongly suggest that receptors with identical HLA-C allele specificity can mediate functions of opposite sign owing to their different transmembrane/cytoplasmic portions.
Biassoni
R
R
Istituto Nazionale per la Ricerca sul Cancro e Centro Biotecnologie Avanzate, Genova, Italy.
Cantoni
C
C
Falco
M
M
Verdiani
S
S
Bottino
C
C
Vitale
M
M
Conte
R
R
Poggi
A
A
Moretta
A
A
Moretta
L
L
D000595:Amino Acid Sequence; D001483:Base Sequence; D002999:Clone Cells; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection
D018076:DNA, Complementary; D015236:HLA-C Antigens; C515078:KIR2DL3 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; C098615:p50 natural killer cell receptor