TY - JOUR
T1 - The CD94/NKG2-A Inhibitory Receptor Complex Is Involved in Natural Killer Cell-Mediated Recognition of Cells Expressing HLA-G1
AU - Pérez-Villar, Juan J.
AU - Melero, Ignacio
AU - Navarro, Francisco
AU - Carretero, Marta
AU - Bellón, Teresa
AU - Llano, Manuel
AU - Colonna, Marco
AU - Geraghty, Daniel E.
AU - López-Botet, Miguel
PY - 1997/6/15
Y1 - 1997/6/15
N2 - Human NK cells bear surface receptors that inhibit their cytolytic activity upon specific recognition of MHC class Ia Ags; little is known about the capacity of class Ib molecules to regulate NK cell function. We have studied the roles of different NK inhibitory receptors in recognition of the class Ib HLA-G. To this end, we analyzed the ability of an HLA-defective tumor cell line (721.221) transfected with the membrane form of HLA-G1, which contains the three external domains, to inhibit the cytolytic activity mediated by a panel of NK clones from several donors. A substantial proportion of peripheral blood NK clones appeared to be significantly inhibited by the HLA-G1-transfected cell line (referred to as .221-G1); nevertheless, no relation was observed between the expression and the function of serologically identifiable Ig-SF receptors (p58/p70) and specific recognition of .221-G1 cells. Moreover, p58 killer cell inhibitory receptor-IgG soluble fusion proteins specifically bound to 721.221 transfectants bearing their corresponding HLA-C ligands, but only a weak reactivity with .221-G1 cells was detectable. By contrast, most NK clones blocked by HLA-G1 expressed the CD94/NKG2-A inhibitory receptor, and moreover, CD94-specific mAbs reconstituted their cytolytic activity comparably to anti-HLA class I mAbs. These data support the idea that the CD94/ NKG2 receptor complex is involved in the recognition of cells expressing HLA-G1.
AB - Human NK cells bear surface receptors that inhibit their cytolytic activity upon specific recognition of MHC class Ia Ags; little is known about the capacity of class Ib molecules to regulate NK cell function. We have studied the roles of different NK inhibitory receptors in recognition of the class Ib HLA-G. To this end, we analyzed the ability of an HLA-defective tumor cell line (721.221) transfected with the membrane form of HLA-G1, which contains the three external domains, to inhibit the cytolytic activity mediated by a panel of NK clones from several donors. A substantial proportion of peripheral blood NK clones appeared to be significantly inhibited by the HLA-G1-transfected cell line (referred to as .221-G1); nevertheless, no relation was observed between the expression and the function of serologically identifiable Ig-SF receptors (p58/p70) and specific recognition of .221-G1 cells. Moreover, p58 killer cell inhibitory receptor-IgG soluble fusion proteins specifically bound to 721.221 transfectants bearing their corresponding HLA-C ligands, but only a weak reactivity with .221-G1 cells was detectable. By contrast, most NK clones blocked by HLA-G1 expressed the CD94/NKG2-A inhibitory receptor, and moreover, CD94-specific mAbs reconstituted their cytolytic activity comparably to anti-HLA class I mAbs. These data support the idea that the CD94/ NKG2 receptor complex is involved in the recognition of cells expressing HLA-G1.
UR - http://www.scopus.com/inward/record.url?scp=0031570502&partnerID=8YFLogxK
M3 - Article
C2 - 9190923
AN - SCOPUS:0031570502
SN - 0022-1767
VL - 158
SP - 5736
EP - 5743
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -