The Journal of Immunology, Vol 159, Issue 8 3875-3882, Copyright © 1997 by American Association of Immunologists

ARTICLES

Molecular basis of HLA-C recognition by p58 natural killer cell inhibitory receptors

J Kim, YJ Chwae, MY Kim, IH Choi, JH Park and SJ Kim
Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea.

NK cells express several inhibitory receptors that recognize class I MHC molecules expressed on target cells. The NK cell inhibitory receptors (KIRs) provide a key regulatory function for NK cells via specific interaction with MHC/peptide complexes, but the molecular details for recognition of class I MHC molecules by KIRs still remain unclear. Here we report cDNA cloning and expression of p58 KIRs and a p50 killer cell activatory receptor (KAR) from a Korean blood donor and demonstrate direct binding between recombinant soluble p58 KIRs and recombinant soluble HLA-C molecules. We identified three p58/p50 killer cell receptors (KAR-K1, KIR-K6, and KIR-K7), which are homologous to p50 cl-39, p58 47.11, and p58 cl-6, respectively. Native gel shift assay revealed that p58 KIR-K6 and KIR-K7 bind both HLA-Cw3 and HLA-Cw6 molecules, but p50 KAR-K1 binds neither of the HLA-C molecules. However, binding of HLA-C molecule by p58 KIR is affected by the antigenic peptide bound on the MHC molecule, suggesting that the p58 KIR binding to the HLA-C molecule may be dependent on the peptide. In addition, the binding interaction requires the presence of both p58 Ig domains, suggesting that the binding mode of HLA-C and p58 KIR may have some similarity to that of the neonatal Fc receptor and the Fc fragment of Ab and may be distinct from that of TCR and MHC.

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