A p70 killer cell inhibitory receptor specific for several HLA-B allotypes discriminates among peptides bound to HLA-B*2705.

Abstract

Natural killer (NK) cells express a repertoire of killer cell inhibitory receptors (KIR) for major histocompatibility complex (MHC) class I molecules. KIR specificity for MHC class I can be broad, as in the case of a single p70 KIR that can recognize several HLA-B allotypes, including HLA-B*2705. On the other hand, recognition of MHC class I can also be highly specific, as in the case of NK clones that recognize HLA-B*2705 in a peptide-specific manner. Most NK cells express multiple KIR sequences. To determine whether the broad and specific types of HLA-B recognition by NK cells reflect the use of different receptors or a property of a single KIR we analyzed the recognition of HLA-B*2705 by the p70 KIR-11, known to recognize several HLA-B allotypes. Vaccinia virus-mediated expression of KIR-11 in NK clones resulted in inhibition by HLA-B*2705 molecules on wild type but not on target cells deficient in the transporter for antigen presentation (TAP). Two peptides (FRYNGLIHR and RRSKEITVR) loaded onto HLA-B*2705 molecules on TAP-deficient cells provided protection from lysis by NK cells expressing KIR-11 but three other B27-specific peptides did not. As the five peptides bound to HLA-B*2705 with similar stability, these data demonstrate that a single KIR specific for several HLA-B allotypes recognizes a subset of peptides bound to HLA-B*2705.

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

“…Such peptides may be produced in response to infection and introduce allosteric changes in HLA-C molecules or enhance the binding of HLA-C molecules by their cognate KIR receptor. Indeed, KIR preference for certain peptides sequences has been previously demonstrated in studies examining NK cell recognition of HLA-B27-expressing target cells (61,62) and in KIR2DL recognition of HLA-C molecules (63,64). However, we consider it unlikely that differential peptide recognition explains the better NK cell response conferred by the KIR2DL3/HLA-C1 compound genotype compared with the KIR2DL1/HLA-C2 compound genotype for the following reasons.…”

A weak association of HLA-B*2702 with Behçet’s disease

“…On the other hand, it has been reported that binding of KIR is dependent on peptide as well as the class I molecule on the target cell. 26,34,35 Conformational changes in class I molecules after binding of certain peptides may influence its KIR binding specificity, and it may be an explanation for the association of only B*2702 with Behçet's disease.…”

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

“…Evidence indicates that KIR3DL1 binds the MHC a1 helix around residues 76-80, with specificity for all Bw4 alleles containing threonine at heavy-chain residue 80 [17]. In the case of HLA-B*2705 at least, KIR3DL1 also has specificity for bound peptide, showing greatest sensitivity for the residue at position 8 [18][19][20].…”