Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function

Makoto Yawata, Nobuyo Yawata, Monia Draghi, Ann Margaret Little, Fotini Partheniou, Peter Parham

Research output: Contribution to journalArticle

370 Citations (Scopus)

Abstract

Interactions between killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands regulate the development and response of human natural killer (NK) cells. Natural selection drove an allele-level group A KIR haplotype and the HLA-C1 ligand to unusually high frequency in the Japanese, who provide a particularly informative population for investigating the mechanisms by which KIR and HLA polymorphism influence NK cell repertoire and function. HLA class I ligands increase the frequencies of NK cells expressing cognate KIR, an effect modified by gene dose, KIR polymorphism, and the presence of other cognate ligand-receptor pairs. The five common Japanese KIR3DLI allotypes have distinguishable inhibitory capacity, frequency of cellular expression, and level of cell surface expression as measured by antibody binding. Although KIR haplotypes encoding 3DL1*001 or 3DL1*005, the strongest inhibitors, have no activating KIR, the dominant haplotype encodes a moderate inhibitor, 3DL1*01502, plus functional forms of the activating receptors 2DL4 and 2DS4. In the population, certain combinations of KIR and HLA class I ligand are overrepresented or underrepresented in women, but not men, and thus influence female fitness and survival. These findings show how KIR-HLA interactions shape the genetic and phenotypic KIR repertoires for both individual humans and the population. JEM

Original languageEnglish
Pages (from-to)633-645
Number of pages13
JournalJournal of Experimental Medicine
Volume203
Issue number3
DOIs
Publication statusPublished - Mar 20 2006

Fingerprint

KIR Receptors
HLA Antigens
Natural Killer Cells
Ligands
Haplotypes
Population
Genetic Selection
Human Development
Alleles

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function. / Yawata, Makoto; Yawata, Nobuyo; Draghi, Monia; Little, Ann Margaret; Partheniou, Fotini; Parham, Peter.

In: Journal of Experimental Medicine, Vol. 203, No. 3, 20.03.2006, p. 633-645.

Research output: Contribution to journalArticle

Yawata, Makoto ; Yawata, Nobuyo ; Draghi, Monia ; Little, Ann Margaret ; Partheniou, Fotini ; Parham, Peter. / Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function. In: Journal of Experimental Medicine. 2006 ; Vol. 203, No. 3. pp. 633-645.
@article{f9a152280e374d7c90c75acfe40531e0,
title = "Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function",
abstract = "Interactions between killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands regulate the development and response of human natural killer (NK) cells. Natural selection drove an allele-level group A KIR haplotype and the HLA-C1 ligand to unusually high frequency in the Japanese, who provide a particularly informative population for investigating the mechanisms by which KIR and HLA polymorphism influence NK cell repertoire and function. HLA class I ligands increase the frequencies of NK cells expressing cognate KIR, an effect modified by gene dose, KIR polymorphism, and the presence of other cognate ligand-receptor pairs. The five common Japanese KIR3DLI allotypes have distinguishable inhibitory capacity, frequency of cellular expression, and level of cell surface expression as measured by antibody binding. Although KIR haplotypes encoding 3DL1*001 or 3DL1*005, the strongest inhibitors, have no activating KIR, the dominant haplotype encodes a moderate inhibitor, 3DL1*01502, plus functional forms of the activating receptors 2DL4 and 2DS4. In the population, certain combinations of KIR and HLA class I ligand are overrepresented or underrepresented in women, but not men, and thus influence female fitness and survival. These findings show how KIR-HLA interactions shape the genetic and phenotypic KIR repertoires for both individual humans and the population. JEM",
author = "Makoto Yawata and Nobuyo Yawata and Monia Draghi and Little, {Ann Margaret} and Fotini Partheniou and Peter Parham",
year = "2006",
month = "3",
day = "20",
doi = "10.1084/jem.20051884",
language = "English",
volume = "203",
pages = "633--645",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function

AU - Yawata, Makoto

AU - Yawata, Nobuyo

AU - Draghi, Monia

AU - Little, Ann Margaret

AU - Partheniou, Fotini

AU - Parham, Peter

PY - 2006/3/20

Y1 - 2006/3/20

N2 - Interactions between killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands regulate the development and response of human natural killer (NK) cells. Natural selection drove an allele-level group A KIR haplotype and the HLA-C1 ligand to unusually high frequency in the Japanese, who provide a particularly informative population for investigating the mechanisms by which KIR and HLA polymorphism influence NK cell repertoire and function. HLA class I ligands increase the frequencies of NK cells expressing cognate KIR, an effect modified by gene dose, KIR polymorphism, and the presence of other cognate ligand-receptor pairs. The five common Japanese KIR3DLI allotypes have distinguishable inhibitory capacity, frequency of cellular expression, and level of cell surface expression as measured by antibody binding. Although KIR haplotypes encoding 3DL1*001 or 3DL1*005, the strongest inhibitors, have no activating KIR, the dominant haplotype encodes a moderate inhibitor, 3DL1*01502, plus functional forms of the activating receptors 2DL4 and 2DS4. In the population, certain combinations of KIR and HLA class I ligand are overrepresented or underrepresented in women, but not men, and thus influence female fitness and survival. These findings show how KIR-HLA interactions shape the genetic and phenotypic KIR repertoires for both individual humans and the population. JEM

AB - Interactions between killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands regulate the development and response of human natural killer (NK) cells. Natural selection drove an allele-level group A KIR haplotype and the HLA-C1 ligand to unusually high frequency in the Japanese, who provide a particularly informative population for investigating the mechanisms by which KIR and HLA polymorphism influence NK cell repertoire and function. HLA class I ligands increase the frequencies of NK cells expressing cognate KIR, an effect modified by gene dose, KIR polymorphism, and the presence of other cognate ligand-receptor pairs. The five common Japanese KIR3DLI allotypes have distinguishable inhibitory capacity, frequency of cellular expression, and level of cell surface expression as measured by antibody binding. Although KIR haplotypes encoding 3DL1*001 or 3DL1*005, the strongest inhibitors, have no activating KIR, the dominant haplotype encodes a moderate inhibitor, 3DL1*01502, plus functional forms of the activating receptors 2DL4 and 2DS4. In the population, certain combinations of KIR and HLA class I ligand are overrepresented or underrepresented in women, but not men, and thus influence female fitness and survival. These findings show how KIR-HLA interactions shape the genetic and phenotypic KIR repertoires for both individual humans and the population. JEM

UR - http://www.scopus.com/inward/record.url?scp=33645070552&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645070552&partnerID=8YFLogxK

U2 - 10.1084/jem.20051884

DO - 10.1084/jem.20051884

M3 - Article

C2 - 16533882

AN - SCOPUS:33645070552

VL - 203

SP - 633

EP - 645

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -