Affiliations 

  • 1 Division of Biomedical Informatics and Personalized Medicine, Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
  • 2 School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia
  • 3 School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia
  • 4 Blood Center of Zhejiang Province, Key Laboratory of Blood Safety Research of Zhejiang Province, Hangzhou, Zhejiang, China
Immunology, 2021 Apr;162(4):389-404.
PMID: 33283280 DOI: 10.1111/imm.13289

Abstract

Killer cell immunoglobulin-like receptors (KIRs) interact with polymorphic human leucocyte antigen (HLA) class I molecules, modulating natural killer (NK) cell functions and affecting both the susceptibility and outcome of immune-mediated diseases. The KIR locus is highly diverse in gene content, copy number and allelic polymorphism within individuals and across geographical populations. To analyse currently under-represented Asian and Pacific populations, we investigated the combinatorial diversity of KIR and HLA class I in 92 unrelated Malay and 75 Malaysian Chinese individuals from the Malay Peninsula. We identified substantial allelic and structural diversity of the KIR locus in both populations and characterized novel variations at each analysis level. The Malay population is more diverse than Malay Chinese, likely representing a unique history including admixture with immigrating populations spanning several thousand years. Characterizing the Malay population are KIR haplotypes with large structural variants present in 10% individuals, and KIR and HLA alleles previously identified in Austronesian populations. Despite the differences in ancestries, the proportion of HLA allotypes that serve as KIR ligands is similar in each population. The exception is a significantly reduced frequency of interactions of KIR2DL1 with C2+ HLA-C in the Malaysian Chinese group, caused by the low frequency of C2+ HLA. One likely implication is a greater protection from preeclampsia, a pregnancy disorder associated with KIR2DL1, which shows higher incidence in the Malay than in the Malaysian Chinese. This first complete, high-resolution, characterization of combinatorial diversity of KIR and HLA in Malaysians will form a valuable reference for future clinical and population studies.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.