Co-evolution of Human Leukocyte Antigen (HLA) Class I Ligands with Killer-Cell Immunoglobulin-Like Receptors (KIR) in a Genetically Diverse Population of Sub-Saharan Africans
Figure 7
Population-specific co-evolution of HLA and KIR.
A. Plotted is the total number of distinct viable receptor:ligand allotype pairs per individual. The viable interactions are shown in Figure 5. The individual with only one unique interaction, KIR2DL2*001/HLA-C*04:01 is homozygous for common HLA (A*23:01, B*44:03, C*04:01) and KIR (KIR2DL2*001, KIR2DL1/S1/S2 negative, KIR3DL1*004 (non-expressed)) haplotypes. B. Shown are the results of a Mantel test for correlation between distance matrices generated from SNP genotypes of HLA-B and KIR3DL1/S1. Distance matrices of genotypes defined by the nine HLA-B residues shown correlate (p = 0.0001) with those of KIR3DL1 position 86 (refers to residues 31, 44 and 86, which are in perfect LD. Presence of leucine at residue 86 disrupts cell-surface expression of KIR3DL1 [57] (Figure S13)). Orange indicates KIR-contacting residues, green indicates LILR binding residue. R83, which is critical for binding to KIR3DL1, is shown in bold [65]. Groups of residues in LD are boxed. C. (Left) shows the group of HLA-C residues (LD194; which distinguish C*07 from the other HLA-C in Ga-Adangbe) whose genotypes correlate with those of KIR2DL2/3 (p = 0.005). (Right) shows the results of Mantel tests performed using the LD194 group, and HLA-C genotypes with them removed (not-LD194). 2DL2 vs. 2DL3 refers to the set of residues that distinguish KIR2DL2 from KIR2DL3, and 2DL2/3 SNPs is the set of residues that vary but do not discriminate KIR2DL2 from KIR2DL3 (See Figure S2). D. Shows the groups of HLA-C and KIR2DL1 residues that correlate with each other. Genotypes defined by HLA-C residues 14 and 49 correlate with those defined by residues 154, 163, 182, 216 and 245 of KIR2DL1. Orange indicates KIR-contacting residues, blue shows residue 245 that disrupts KIR2DL1 function [73]. B–D. Allotype names are at the left and where the motif is identical, only the most common allotype is shown.