PMID- 28352266
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230801
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - Canonical and Cross-reactive Binding of NK Cell Inhibitory Receptors to HLA-C 
      Allotypes Is Dictated by Peptides Bound to HLA-C.
PG  - 193
LID - 10.3389/fimmu.2017.00193 [doi]
LID - 193
AB  - BACKGROUND: Human natural killer (NK) cell activity is regulated by a family of 
      killer cell immunoglobulin-like receptors (KIRs) that bind human leukocyte 
      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 (Lys(80)). KIR2DL2 and KIR2DL3 bind HLA-C 
      alleles of group C1 (Asn(80)). 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 inhibitory KIR binding was investigated taking 
      advantage of the fact that HLA-C*05:01 (HLA-C group 2, C2) and HLA-C*08:02 (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-C*05:01 and used to test the peptide dependence of KIR2DL1 and KIR2DL2/3 
      binding to HLA-C*05:01 and HLA-C*08:02 and subsequent impact on NK cell function. 
      Specific binding of KIR2DL1 to the C2 allotype occurred with the majority of 
      peptides tested. In contrast, KIR2DL2/3 binding to the C1 allotype occurred with 
      only a subset of peptides. Cross-reactive binding of KIR2DL2/3 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. CONCLUSION: KIR2DL2/3 binding to C1 is more 
      peptide selective than that of KIR2DL1 binding to C2, providing an explanation 
      for KIR2DL3-C1 interactions appearing weaker than KIR2DL1-C2. In addition, 
      cross-reactive binding of KIR is characterized by even higher peptide 
      selectivity. We demonstrate a hierarchy of functional peptide selectivity of 
      KIR-HLA-C interactions with relevance to NK cell biology and human disease 
      associations. This selective peptide sequence-driven binding of KIR provides a 
      potential mechanism for pathogen as well as self-peptide to modulate NK cell 
      activation through altering levels of inhibition.
FAU - Sim, Malcolm J W
AU  - Sim MJ
AD  - Laboratory of Immunogenetics, National Institute of Allergy and Infectious 
      Diseases, NIH, Rockville, MD, USA; Lung Immunology Group, Department of Medicine, 
      Imperial College London, London, UK.
FAU - Malaker, Stacy A
AU  - Malaker SA
AD  - Department of Chemistry, University of Virginia, Charlottesville, VA, USA; 
      Department of Chemistry, Stanford University, Stanford, CA, USA.
FAU - Khan, Ayesha
AU  - Khan A
AD  - Lung Immunology Group, Department of Medicine, Imperial College London , London , 
      UK.
FAU - Stowell, Janet M
AU  - Stowell JM
AD  - Lung Immunology Group, Department of Medicine, Imperial College London , London , 
      UK.
FAU - Shabanowitz, Jeffrey
AU  - Shabanowitz J
AD  - Department of Chemistry, University of Virginia , Charlottesville, VA , USA.
FAU - Peterson, Mary E
AU  - Peterson ME
AD  - Laboratory of Immunogenetics, National Institute of Allergy and Infectious 
      Diseases, NIH , Rockville, MD , USA.
FAU - Rajagopalan, Sumati
AU  - Rajagopalan S
AD  - Laboratory of Immunogenetics, National Institute of Allergy and Infectious 
      Diseases, NIH , Rockville, MD , USA.
FAU - Hunt, Donald F
AU  - Hunt DF
AD  - Department of Chemistry, University of Virginia, Charlottesville, VA, USA; 
      Department of Pathology, University of Virginia, Charlottesville, VA, USA.
FAU - Altmann, Daniel M
AU  - Altmann DM
AD  - Lung Immunology Group, Department of Medicine, Imperial College London , London , 
      UK.
FAU - Long, Eric O
AU  - Long EO
AD  - Laboratory of Immunogenetics, National Institute of Allergy and Infectious 
      Diseases, NIH , Rockville, MD , USA.
FAU - Boyton, Rosemary J
AU  - Boyton RJ
AD  - Lung Immunology Group, Department of Medicine, Imperial College London , London , 
      UK.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - R01 AI033993/AI/NIAID NIH HHS/United States
GR  - R37 AI033993/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20170314
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5348643
OTO - NOTNLM
OT  - human leukocyte antigen
OT  - immunogenetics
OT  - innate immunity
OT  - killer cell Ig-like receptors
OT  - natural killer cell
EDAT- 2017/03/30 06:00
MHDA- 2017/03/30 06:01
PMCR- 2017/01/01
CRDT- 2017/03/30 06:00
PHST- 2017/01/03 00:00 [received]
PHST- 2017/02/09 00:00 [accepted]
PHST- 2017/03/30 06:00 [entrez]
PHST- 2017/03/30 06:00 [pubmed]
PHST- 2017/03/30 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.00193 [doi]
PST - epublish
SO  - Front Immunol. 2017 Mar 14;8:193. doi: 10.3389/fimmu.2017.00193. eCollection 
      2017.