Implications of HLA-E allele expression and different HLA-E ligand diversity for the regulation of NK cells

The interaction of HLA-E: with CD94/NKG2A is dependant on the binding of HLA class I signal sequence derived peptides to HLA-E. In the caucasoid population two HLA-E alleles are observed at equal frequencies. I-Ic re are study the functional differences between the two HLA-E molecules with regard to cell surface expression, peptide binding, and potential to inhibit lytic activity of a CD94/NKG2A(+) NK cell line. In contrast to the HLA-E-R allele, the HLA-E-G allele shows considerable cell surface expression even in the absence of endogenous HLA class I signal sequence derived HLA-E ligands. Eighteen HLA-E allele/HLA-E ligand combinations were analyzed. No correlation between cell surface expression of HLA-E and NK cell inhibition was observed. The peptides present in the signal sequences of HLA-B15, -Cw0402, and -Cw7 bound to both HLA-E alleles but did not lead to an inhibition of NK cell lysis. In our experimental system the peptides A2 and G were not effective with regard to NK cell inhibition when bound to the HLA-E-R allele. These results may be of functional significance particularly in the placenta where the only HLA-E ligands are derived from HLA-G and -C. (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.