Molecular and functional characterization of IRp60, a member of the immunoglobulin superfamily that functions as an inhibitory receptor in human NK cells.
In this study we describe the functional and molecular characterization of IRp60 (inhibitory receptor protein 60), an inhibitory receptor expressed on all human NK cells. The IRp60 molecule has been identified by the generation of three novel monoclonal antibodies (mAb). Cross-linking of IRp60 by specific mAb strongly inhibits the spontaneous cytotoxicity of NK cells as well as the NK-mediated cytolytic activity induced via different non-HLA-specific or HLA-specific activating receptors. IRp60 is a 60-kDa glycoprotein that, upon sodium pervanadate treatment, becomes tyrosine phosphorylated and associates with the SH2-containing phosphatases SHP-1 and SHP-2. The IRp60 gene is located on human chromosome 17 and encodes a molecule belonging to the immunoglobulin (Ig) superfamily characterized by a single V-type Ig-like domain in the extracellular portion. The cytoplasmic tail contains three classical immunoreceptor tyrosine-based inhibitory motifs. Southern blot analysis revealed cross-hybridization with monkey and mouse genomic DNA, thus suggesting that IRp60 may be conserved among different species. Moreover, based on the use of different anti-IRp60 mAb, we could identify two IRp60 allelic variants. Since IRp60 is also expressed by other cell types, including T cell subsets, monocytes and granulocytes, it may play a more general role in the negative regulation of different leukocyte populations.
Cantoni
C
C
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy.
Bottino
C
C
Augugliaro
R
R
Morelli
L
L
Marcenaro
E
E
Castriconi
R
R
Vitale
M
M
Pende
D
D
Sivori
S
S
Millo
R
R
Biassoni
R
R
Moretta
L
L
Moretta
A
A
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D015342:DNA Probes; D018076:DNA, Complementary / Q000032:analysis; D000882:Haplorhini; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics; D007694:Killer Cells, Natural / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054340:Receptors, KIR; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; C515070:CD300A protein, human; D015342:DNA Probes; D018076:DNA, Complementary; D007136:Immunoglobulins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D054340:Receptors, KIR