Co-evolution of NK receptors and HLA ligands in humans is driven by reproduction

Summary Allogeneic individuals co‐exist during pregnancy in eutherian mammals. Maternal and fetal cells intermingle at the site of placental attachment in the uterus, where the arteries are remodeled to supply the fetus with oxygen and nutrients. This access by placental cells to the maternal supply...

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Published in:Immunological reviews Vol. 267; no. 1; pp. 283 - 297
Main Authors: Moffett, Ashley, Colucci, Francesco
Format: Journal Article
Language:English
Published: England Blackwell Publishing Ltd 01.09.2015
Subjects:
birth weight
Evolution, Molecular
Female
HLA
HLA-C Antigens - genetics
HLA-C Antigens - immunology
Humans
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
KIR
Ligands
placenta
Polymorphism, Genetic - genetics
Polymorphism, Genetic - immunology
Pregnancy
Receptors, KIR - genetics
Receptors, KIR - immunology
trophoblast
Trophoblasts - immunology
Trophoblasts - metabolism
birth weight
placenta
HLA
trophoblast
KIR
ISSN:0105-2896, 1600-065X, 1600-065X
Online Access:Get full text
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Summary:Summary Allogeneic individuals co‐exist during pregnancy in eutherian mammals. Maternal and fetal cells intermingle at the site of placental attachment in the uterus, where the arteries are remodeled to supply the fetus with oxygen and nutrients. This access by placental cells to the maternal supply line determines the growth and birth weight of the baby and is subject to stabilizing selection. Invading placental trophoblast cells express human leukocyte antigen class I ligands (HLA‐E, HLA‐G, and HLA‐C) for receptors on maternal uterine natural killer (NK) and myelomonocytic cells, CD94/NKG2, leukocyte immunoglobulin‐like receptor (LILR), and killer immunoglobulin receptor (KIR). Of these, only the KIR/HLA‐C system is highly polymorphic. Different combinations of maternal KIR and fetal HLA‐C variants are correlated with low birth weight and pre‐eclampsia or high birth weight and obstructed labor, the two extremes of the obstetric dilemma. This situation has arisen because of the evolution of bipedalism and subsequently, in the last million years, larger brains. At this point, the human system began to reach a balance between KIR A and KIR B haplotypes and C1 and C2 epitopes of HLA‐C alleles that reflects a functional compromise between the competing demands of immunity and reproduction.
Bibliography:Centre for Trophoblast Research
ArticleID:IMR12323
ark:/67375/WNG-FGWN4BQV-8
istex:EA772E997192A257496EEC1F99156D3DA9AC2B25
Wellcome Trust
University of Cambridge
King's College, Cambridge
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
ISSN:0105-2896
1600-065X
1600-065X
DOI:10.1111/imr.12323