N. Lee et al., HLA-E IS A MAJOR LIGAND FOR THE NATURAL-KILLER INHIBITORY RECEPTOR CD94 NKG2A/, Proceedings of the National Academy of Sciences of the United Statesof America, 95(9), 1998, pp. 5199-5204
We previously showed that the availability of a nonamer peptide derive
d from certain HLA class I signal sequences is a necessary requirement
for the stabilization of endogenous HLA-E expression on the surface o
f 721.221 cells. This led us to examine the ability of HLA-E to protec
t HLA class I transfectants from natural killer (NK) cell-mediated lys
is, It was possible to implicate the CD94/NKG2A complex as an inhibito
ry receptor recognizing this class Ib molecule by using as target a .2
21 transfectant selectively expressing surface HLA-E. HLA-E had no app
arent inhibitory effect mediated through the identified Ig superfamily
(Ig-SF) human killer cell inhibitory receptors or ILT2/LIR1, Further
studies of CD94/NKG2+ NK cell-mediated recognition of .221 cells trans
fected with different HLA class I allotypes (i.e., -Cw4, -Cw3, -B7) co
nfirmed that the inhibitory interaction was mediated by CD94/NKG2A rec
ognizing the surface HLA-E molecule, because only antibodies directed
against either HLA-E, CD94, or CD94/NKG2A specifically restored lysis,
Surface stabilization of HLA-E in cold-treated .221 cells loaded with
appropriate peptides was sufficient to confer protection, resulting f
rom recognition of the HLA class Ib molecule by the CD94/NKG2A inhibit
ory receptor. Consistent with the prediction that the ligand for CD94/
NKG2A is expressed ubiquitously, our examination of HLA-E antigen dist
ribution indicated that it is detectable on the surface of a wide vari
ety of cell types.