Peptide selectivity discriminates NK cells from KIR2DL2-and KIR2DL3-positive individuals
Author(s)
Type
Journal Article
Abstract
Natural killer cells are controlled by peptide selective inhibitory receptors for MHC class I, including the killer cell immunoglobulin-like receptors (KIRs). Despite having similar ligands, KIR2DL2 and KIR2DL3 confer different levels of protection to infectious disease. To investigate how changes in peptide repertoire may differentially affect NK cell reactivity, NK cells from KIR2DL2 and KIR2DL3 homozygous donors were tested for activity against different combinations of strong inhibitory (VAPWNSFAL), weak inhibitory (VAPWNSRAL), and antagonist peptide (VAPWNSDAL). KIR2DL3-positive NK cells were more sensitive to changes in the peptide content of MHC class I than KIR2DL2-positive NK cells. These differences were observed for the weakly inhibitory peptide VAPWNSRAL in single peptide and double peptide experiments (p < 0.01 and p < 0.03, respectively). More significant differences were observed in experiments using all three peptides (p < 0.0001). Mathematical modeling of the experimental data demonstrated that VAPWNSRAL was dominant over VAPWNSFAL in distinguishing KIR2DL3- from KIR2DL2-positive donors. Donors with different KIR genotypes have different responses to changes in the peptide bound by MHC class I. Differences in the response to the peptide content of MHC class I may be one mechanism underlying the protective effects of different KIR genes against infectious disease.
Date Issued
2014-11-29
Date Acceptance
2014-10-24
Citation
European Journal of Immunology, 2014, 45 (2), pp.492-500
ISSN
1521-4141
Publisher
Wiley-VCH Verlag
Start Page
492
End Page
500
Journal / Book Title
European Journal of Immunology
Volume
45
Issue
2
Copyright Statement
© 2014 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly
cited.
cited.
Sponsor
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000349625400018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
093465/Z/10/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Killer-cell immunoglobulin-like receptors
MHC class I
Natural killer cells
Peptide
Peptide selectivity
IMMUNOGLOBULIN-LIKE RECEPTOR
NATURAL-KILLER-CELLS
C VIRUS-INFECTION
HLA-C
CLASS-I
INHIBITORY RECEPTORS
KIR GENES
RESPONSES
BINDING
ACTIVATION
Amino Acid Sequence
Cell Degranulation
Gene Expression Regulation
Genotype
HLA-C Antigens
Homozygote
Humans
Killer Cells, Natural
Ligands
Models, Statistical
Molecular Sequence Data
Peptides
Primary Cell Culture
Protein Binding
Receptors, KIR2DL2
Receptors, KIR2DL3
Structure-Activity Relationship
Publication Status
Published