M. Llano et al., HLA-E-BOUND PEPTIDES INFLUENCE RECOGNITION BY INHIBITORY AND TRIGGERING CD94 NKG2 RECEPTORS - PREFERENTIAL RESPONSE TO AN HLA-G-DERIVED NONAMER/, European Journal of Immunology, 28(9), 1998, pp. 2854-2863
The HLA-E class Ib molecule constitutes a major ligand for the lectin-
like CD94/NKG2 natural killer (NK) cell receptors. Specific HLA class
I leader sequence-derived nonapeptides bind to endogenous HLA-E molecu
les in the HLA-defective cell line 721.221, inducing HLA-E surface exp
ression, and promote CD94/NKG2A-mediated recognition. We compared the
ability of NK clones which expressed either inhibitory or activating C
D94/NKG2 receptors to recognize HLA-E molecules on the surface of 721.
221 cells loaded with a panel of synthetic nonamers derived from the l
eader sequences of most HLA class I molecules. Our results support the
notion that the primary structure of the HLA-E-bound peptides influen
ces CD94/NKG2-mediated recognition, beyond their ability to stabilize
surface HLA-E. Further, CD94/NKG2A(+) NK clones appeared more sensitiv
e to the interaction with most HLA-E-peptide complexes than did effect
or cells expressing the activating CD94/NKG2C receptor. However, a sig
nificant exception to this pattern was HLA-E loaded with the HLA-G-der
ived nonamer. This complex triggered cytotoxicity very efficiently ove
r a wide range of peptide concentrations, suggesting that the HLA-E/G-
nonamer complex interacts with the CD94/NKG2 triggering receptor with
a significantly higher affinity. These results raise the possibility t
hat CD94/NKG2-mediated recognition of HLA-E expressed on extravillous
cytotrophoblasts plays an important role in maternal-fetal cellular in
teractions.