Variations in killer-cell immunoglobulin-like receptor and human leukocyte antigen genes and immunity to malaria

Malaria is one of the deadliest infectious diseases in the world. Immune responses to Plasmodium falciparum malaria vary among individuals and between populations. Human genetic variation in immune system genes is likely to play a role in this heterogeneity. Natural killer (NK) cells produce inflammatory cytokines in response to malaria infection, kill intraerythrocytic Plasmodium falciparum parasites by cytolysis, and participate in the initiation and development of adaptive immune responses to plasmodial infection. These functions are modulated by interactions between killer-cell immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA). Therefore, variations in KIR and HLA genes can have a direct impact on NK cell functions. Understanding the role of KIR and HLA in immunity to malaria can help to better characterize antimalarial immune responses. In this review, we summarize the different KIR and HLA so far associated with immunity to malaria.This work was supported through the DELTAS Africa Initiative (Grant no. 107743), that funded Stephen Tukwasibwe through PhD fellowship award, and Annettee Nakimuli through group leader award. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Science (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743) and the UK government. Francesco Colucci is funded by Wellcome Trust grant 200841/Z/16/Z. The project received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. 695551) for James Traherne and John Trowsdale. Jyothi Jayaraman is a recipient of fellowship from the Centre for Trophoblast Research

Full-length sequence of KIR3DL1*01501 allele found in Sub-Saharan Africa by long-range sequencing.

Full-length KIR3DL1*01501 differing from KIR3DL1*0150201 with 10 SNPs and 2 nucleotide deletion in intron 7

Description of a novel KIR3DL1*0150211 allele isolated using molecular techniques.

KIR3DL1*0150211 differs from KIR3DL1*0150201 with six single nucleotide polymorphisms in introns 3, 4, 5, and 6

Full-length genomic sequence of a new KIR3DL1*0150203 allele.

KIR3DL1*0150203 allele differs from KIR3DL1*0150201 at 3037G>A, 4115A>G, 6053G>C, 8034A>G, 10723C>A, and 10747C>G

Identification of KIR3DL1*0050103 by the sequence-based techniques.

The new KIR3DL1*0050103 allele has a mutation at nucleotide position 6709 (C>T) in intron 5. © 2013 John Wiley and Sons A/S

A novel KIR3DL1*0200102 allele isolated from a West African donor by sequence-based typing.

KIR3DL1*0200102 allele differs from KIR3DL1*0200101 with four single nucleotide polymorphisms in introns 5 and 6, respectively

Two novel KIR3DL1 alleles, 3DL1*0150205 and 3DL1*0150206, identified by full-length DNA sequencing.

KIR3DL1*0150205 and KIR3DL1*0150206 alleles have five and six mutations, respectively, compared with KIR3DL1*0150201

Description of a novel KIR3DL1*0050104 allele identified using sequence-based techniques.

KIR3DL1*0050104 allele differs from KIR3DL1*0050101 at nucleotide positions 6709C>T (intron 5) and 11365A>G (intron 6)

Full-length KIR3DL1*022 detected in an African donor.

KIR3DL1*022 is significantly different from the most common West African allele - KIR3DL1*01501

Killer-cell immunoglobulin-like receptor gene 3DL1*077 isolated using long-range sequence-based techniques.

KIR3DL1*077 gene has two non-synonymous mutations (exon 5) and six intronic changes compared to KIR3DL1*0150201