HLA-G recognition by human natural killer cells. Involvement of CD94 both as inhibitory and as activating receptor complex

被引:88
作者
Pende, D
Sivori, S
Accame, L
Pareti, L
Falco, M
Geraghty, D
LeBouteiller, P
Moretta, L
Moretta, A
机构
[1] CTR BIOTECNOL AVANZATE,IST SCI TUMORI,I-16132 GENOA,ITALY
[2] UNIV GENOA,IST ISTOL & EMBRIOL GEN,GENOA,ITALY
[3] FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104
[4] CHU PURPAN,INSERM,U395,TOULOUSE,FRANCE
[5] UNIV GENOA,IST PATOL GEN,GENOA,ITALY
[6] UNIV BRESCIA,DIPARTIMENTO SCI BIOMED & BIOTECHNOL,I-25121 BRESCIA,ITALY
关键词
HLA-G; CD94; NKG2A; natural killer cell receptors;
D O I
10.1002/eji.1830270809
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The lack of classical human histocompatibility leukocyte antigen (HLA) molecules in human placenta prevents the recognition and lysis by maternal T lymphocytes but poses the problem of susceptibility to natural killer (NK) cell-mediated lysis. The nonclassical HLA class I molecule HLA-G may mediate protection from NK cells. NK cells are known to express a number of HLA class I-specific inhibitory receptors. These include members of the immunoglobulin (Ig) superfamily (p58, p70, p140), characterized by a defined allele specificity, and CD94/NKG2A with a broad specificity for different HLA class I molecules. We analyzed a series of NK cell clones derived from normal peripheral blood expressing different NK receptors (NKR). Clones were analyzed for their cytolytic activity against the HLA class I-negative 221 cell line either untransfected or transfected with HLA-G (221/G) or other informative alleles, as control. All clones expressing CD94/NKG2A [as identified by the Z199 monoclonal antibody (mAb)] displayed a markedly reduced cytolytic activity against 221/G. Moreover, mAb directed to the CD94/NKG2A complex completely restored target cell lysis. Among NKG2A-negative NK clones, different functional patterns could be detected. Clones expressing inhibitory receptors belonging to the Ig superfamily lysed 221/G target cells with equal or higher efficiency than untransfected 221 cells. These data indicated that p58, p70 and p140 do not function as HLA-G-specific inhibitory NKR, and that HLA-G-specific activating NKR also exist. Further analysis indicated that in these clones (characterized by the CD94(+)/NKG2A(-) phenotype) mAb specific for CD94, but not for the other NKR, reversed the activating effect. Infrequent clones were also isolated that, in spite of the lack of CD94/NKG2A, displayed HLA-G specificity, thus suggesting the existence of a different, still unknown NKR.
引用
收藏
页码:1875 / 1880
页数:6
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