Imperial College London


Faculty of MedicineDepartment of Infectious Disease

Professor of Immunology and Respiratory Medicine







8N22Commonwealth BuildingHammersmith Campus






BibTex format

author = {SIM, M and Malaker, S and Khan, A and Stowell, J and Shabanowitz, J and Peterson, M and Rajagopalan, S and Hunt, D and Altmann, D and LONG, E and Boyton, RJ},
doi = {10.3389/fimmu.2017.00193},
journal = {Frontiers in Immunology},
title = {Canonical and cross-reactive binding of NK cell inhibitory receptors to HLA-C allotypes is dictated by peptides bound to HLA-C},
url = {},
volume = {8},
year = {2017}

RIS format (EndNote, RefMan)

AB - Background.Human natural killer (NK) cell activity is regulated by a family of killer-cell Ig-like receptors (KIR) that bind human leucocyte antigen (HLA) class I. Combinations of KIR and HLA genotypes are associated with disease, including susceptibility to viral infection and disorders of pregnancy. KIR2DL1 binds HLA-C alleles of group C2 (Lys80). KIR2DL2 and KIR2DL 3 bind HLA-C alleles of group C1 (Asn80). However, this model cannot explain HLA-C allelic effects in disease or the impact of HLA-bound peptides. The goal of this study was to determine the extent to which the endogenous HLA-C peptide repertoire can influence the specific binding of inhibitory KIR to HLA-C allotypes.Results.The impact of HLA-C bound peptide on inhibit ory KIR binding was investigated taking advantage of the fact that HLA-C05:01 (HLA-C group 2, C2) and HLA-C08:02 (HLA-C group 1, C1) have identical sequences apart from the key KIR specificity determining epitope at residues 77 and 80. Endogenous peptides were eluted from HLA-C05:01 and used to test the peptide dependence of KIR2DL1 and KIR2DL2/3 binding to HLA-C05:01 and HLA-C08:02 and subsequent impact on NK cell function. Specific binding of KIR2DL1 to the C2 allotype occurred with the majority of peptides tested. In contrast, KIR2DL 2/3 binding to the C1 allotype occurred with only a subset of peptides. Cross-reactive binding of KIR2DL 2/3 with the C2 allotype was restricted to even fewer peptides. Unexpectedly, two peptides promoted binding of the C2 allotype-specific KIR2DL1 to the C1 allotype. We showed that presentation of endogenous peptides or HIV Gag peptides by HLA-C can promote KIR cross-reactive binding.Conclusions.KIR2DL2/3 binding to C1 is more peptide selective than that of KIR2DL1binding to C2, providing an explanation for KIR2DL3–C1 interactions appearing weaker than KIR2DL1–C2. In addition, cros
AU - Malaker,S
AU - Khan,A
AU - Stowell,J
AU - Shabanowitz,J
AU - Peterson,M
AU - Rajagopalan,S
AU - Hunt,D
AU - Altmann,D
AU - Boyton,RJ
DO - 10.3389/fimmu.2017.00193
PY - 2017///
SN - 1664-3224
TI - Canonical and cross-reactive binding of NK cell inhibitory receptors to HLA-C allotypes is dictated by peptides bound to HLA-C
T2 - Frontiers in Immunology
UR -
UR -
VL - 8
ER -