KIR diversity in Māori and Polynesians: populations in which HLA-B is not a significant KIR ligand

Abstract

HLA class I molecules and killer cell immunoglobulin-like receptors (KIR) form a diverse system of ligands and receptors that individualize human immune systems in ways that improve the survival of individuals and populations. Human settlement of Oceania by island-hopping East and Southeast Asian migrants started ~3,500 years ago. Subsequently, New Zealand was reached ~750 years ago by ancestral Māori. To examine how this history impacted KIR and HLA diversity, and their functional interaction, we defined at high resolution the allelic and haplotype diversity of the 13 expressed KIR genes in 49 Māori and 34 Polynesians. Eighty KIR variants, including four ‘new’ alleles, were defined; as were 35 centromeric and 22 telomeric KIR region haplotypes, which combine to give >50 full-length KIR haplotypes. Two new and divergent variant KIR form part of a telomeric KIR haplotype, which appears derived from Papua New Guinea and was probably obtained by the Asian migrants en route to Polynesia. Māori and Polynesian KIR are very similar, but differ significantly from African, European, Japanese and Amerindian KIR. Māori and Polynesians have high KIR haplotype diversity with corresponding allotype diversity being maintained throughout the KIR locus. Within the population each individual has a unique combination of HLA class I and KIR. Characterizing Māori and Polynesians is a paucity of HLA-B allotypes recognized by KIR. Compensating for this deficiency are high frequencies (>50%) of HLA-A allotypes recognized by KIR. These HLA-A allotypes are ones that modern humans likely acquired from archaic humans at a much earlier time.

Polymorphic HLA-C Receptors Balance the Functional Characteristics of KIR Haplotypes

“…The amino-acid substitutions that distinguish representative members of the four clades are shown in Figure 1B. Clade 1 comprises ten KIR2DL1*001 -like alleles (Figure 1B), seven of which have been mapped to KIR haplotypes (29, 38-43). Five of the seven are present in Cen A , the centromeric region of KIR A haplotypes (Figure 2).…”

“…Cen B haplotypes that lack the KIR2DL1 gene ( KIR2DL1 blank) are widespread and associated with KIR2DL2*003, KIR2DL2*001 and KIR2DL2*005 (Table I) (38-43, 46). These Cen B haplotypes retain some capacity to recognize C2 because their associated KIR2DL2 allotypes cross-react with C2 (Figure S3B).…”

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

“…In this scenario one may expect specific alleles or combinations to be beneficial for resisting specific infections, or stimulating immune‐mediated disease 44. This combinatorial diversity is amplified by hosting the KIR and HLA genes on separate chromosomes, and the result is many millions of different cognate KIR / HLA class I genotypes, tending to individuality 45, 46. Hence, through evolving multiple genetic mutations in the KIR locus, the human population probably generates and maintains considerable diversity in immunity to evolutionarily nimble and diverse pathogens 17.…”

“…66 Hence, in both populations it appears that KIR have been able to respond rapidly and specifically to HLA class I frequency changes (of unknown aetiology). In contrast, in the Māori of New Zealand, a very low frequency of HLA‐B allotypes expressing the Bw4 motif (again of unknown aetiology) has been countered by an increase in frequency of HLA‐A allotypes that express KIR ligands 46. Such studies of human populations at high resolution reveal functionally important changes occurring on a fine scale, the sum of which throughout human evolution has resulted in the strong signature of balancing selection throughout the KIR locus.…”

Genetic Ancestry and Health

“…These systems include HLA, MICA, KIR, blood group, cytokine, HNA and HPA [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. These new datasets not only provide special insights into the ancestry of these people, but also is of significant value in health; as recently reviewed by [21][22].…”