Possible KIR-driven genetic pressure on the genesis and maintenance of specific HLA-A,B haplotypes as functional genetic blocks

Genes and Immunity
C CapittiniM Martinetti

Abstract

The HLA genomic structure underlines the permanence of fixed haplotypes transmitted in blocks as allelic combinations. One of the most discussed concerns is how and why such a strong linkage between HLA alleles has been maintained for so long. We hypothesized a possible KIR-driven pressure in the genesis of specific HLA-A,B haplotypes. Certain HLA-A and -B molecules are ligands for the same KIR receptors through the Bw4 binding motif spanning residues 77-83 in the α1 domain. We analyzed the HLA-A and -B genomic types of 9897 Caucasian people (3533 newborns and 6364 adults) subdividing them according to the presence/absence of the HLA-B Bw4 serological epitope. For each HLA-B Bw4- and Bw6-cross-reactive group, we evaluated the presence/absence of HLA-A ligands for KIR3DL1 (HLA-A*23, HLA-A*24, HLA-A*32) and KIR3DL2 (HLA-A*03, HLA-A*11). The frequency of HLA-A KIR ligands significantly increased moving from the HLA-B Bw4/Bw4 to the HLA-B Bw4/Bw6 and the HLA-B Bw6/Bw6 groups among both newborns and adults (P<0.0001). Here, we suggest that, when the HLA-B KIR-ligand motif is lacking, the HLA-A KIR-ligand might have a vicarious role in controlling the natural killer cell-mediated innate immune response. Basing upon this compensatory ...Continue Reading

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Citations

Mar 2, 2013·PloS One·Danillo Gardenal AugustoMaria Luiza Petzl-Erler
Nov 15, 2013·Proceedings of the National Academy of Sciences of the United States of America·Bridget S PenmanSunetra Gupta
Mar 11, 2015·Journal of the European Academy of Dermatology and Venereology : JEADV·V BrazzelliG Borroni
Jun 24, 2015·Human Genetics·Danillo G Augusto, Maria Luiza Petzl-Erler
Dec 2, 2017·European Journal of Immunology·Cristina CapittiniMiryam Martinetti
Mar 7, 2021·Viruses·Gloria Pérez-RubioRamcés Falfán-Valencia

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