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Human KIR repertoires: shaped by genetic diversity and evolution
Author(s) -
Manser Angela R.,
Weinhold Sandra,
Uhrberg Markus
Publication year - 2015
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12316
Subject(s) - biology , human leukocyte antigen , haplotype , repertoire , genetics , gene , receptor , clone (java method) , immunology , antigen , allele , physics , acoustics
Summary Killer cell immunoglobulin‐like receptors ( KIR s) on natural killer ( NK ) cells are crucially involved in the control of cancer development and virus infection by probing cells for proper expression of HLA class I. The clonally distributed expression of KIR s leads to great combinatorial diversity that develops in the presence of the evolutionary older CD 94/ NKG 2A receptor to create highly stochastic but tolerant repertoires of NK cells. These repertoires are present at birth and are subsequently shaped by an individuals’ immunological history toward recognition of self. The single most important factor that shapes functional NK cell repertoires is the genetic diversity of KIR , which is characterized by the presence of group A and B haplotypes with complementary gene content that are present in all human populations. Group A haplotypes constitute the minimal genetic entity that provides high affinity recognition of all major human leukocyte antigen class I‐encoded ligands, whereas group B haplotypes contribute to the diversification of NK cell repertoires by providing sets of stimulatory KIR genes that modify NK cell responses. We suggest a cooperative model for the balancing selection of A and B haplotypes, which is driven by the need to provide a suitable corridor of repertoire complexity in which A/A individuals with only 16 different KIR combinations coexist with A/B and B/B donors expressing up to 2048 different clone types.