Imperial College London
Alternate

ProfessorRosemaryBoyton

Faculty of Medicine, Department of Infectious Disease

Professor of Immunology and Respiratory Medicine
 
 
 
//

Contact

 

r.boyton

 
 
//

Location

 

8N22Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{SIM:2017:10.3389/fimmu.2017.00193,
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 = {http://dx.doi.org/10.3389/fimmu.2017.00193},
volume = {8},
year = {2017}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
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  - SIM,M
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  - LONG,E
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  - http://dx.doi.org/10.3389/fimmu.2017.00193
UR  - http://hdl.handle.net/10044/1/44492
VL  - 8
ER  -
Download