1. Possible KIR-driven genetic pressure on the genesis and maintenance of specific HLA-A,B haplotypes as functional genetic blocks
- Author
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Ilaria Sbarsi, C. Pizzochero, M. Martinetti, A. L. Cremaschi, Carmine Tinelli, F. Garlaschelli, Laura Salvaneschi, C. Badulli, Annamaria Pasi, C Monti, M. Guarene, and Cristina Capittini
- Subjects
Adult ,Immunology ,Human leukocyte antigen ,Biology ,Ligands ,Epitope ,White People ,Gene Frequency ,Receptors, KIR ,Genetics ,Humans ,Allele ,Receptor ,Genetics (clinical) ,Immunity, Cellular ,HLA-A Antigens ,Models, Genetic ,Haplotype ,Infant, Newborn ,Models, Immunological ,Immunity, Innate ,HLA-A ,Killer Cells, Natural ,KIR3DL2 ,Haplotypes ,Italy ,HLA-B Antigens ,KIR3DL1 - 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
- Published
- 2012