A combined genotype of KIR3DL1 high expressing alleles and HLA-B*57 is associated with a reduced risk of HIV infection

Abstract

Coexpression of 3DL1*h/*y and B*57, which has been associated with a reduced risk of progressing to AIDS in HIV-infected individuals also lowers the risk of HIV infection in exposed uninfected individuals.

HIV Protective KIR3DL1 and HLA-B Genotypes Influence NK Cell Function Following Stimulation with HLA-Devoid Cells

“…As shown in Fig. 1 Certain KIR3DL1 and HLA-Bw4 genotype combinations have been shown to be associated with time to AIDS and VL set point (9) or have been reported to be associated with a reduced risk of HIV infection in EUs (12). The 3DL1/Bw4 genetic combination that has been most strongly associated with these HIV outcomes is *h/*y+B*57 and this may be because this combined genotype confers a unique NK cell functional profile.…”

“…This genotype is composed of a 3DL1 genotype termed 3DL1*h/*y (i.e., lacking 3DL1*l alleles) with HLA-B*57, an HLA-Bw4 allele with an isoleucine at position 80 (i.e., Bw4-80I). In line with these findings, our group recently reported an association between carrying the *h/*y+B*57 combination with resistance to infection in a population of HIV exposed uninfected (EU) individuals (12). However, although these data support a role for NK cells in control of HIV that varies depending on carriage of *h/*y+B*57, there are few studies linking this KIR/HLA combined genotype to improved antiviral NK cell function.…”

“…KIR3DL/S1 generic genotyping was performed by PCR using two pairs of specific primers for amplification of either KIR3DL1 or KIR3DS1 as previously described (13). KIR3DL1 allotyping was peformed by sequencing KIR3DL1 exons as previously described (12). Single nucleotide polymorphisms corresponding to the 3DL1 alleles were identified by aligning the sequenced DNA to a reference consensus sequence consisting of a contig of 3DL1 cDNA sequences.…”

“…These subtle variations could explain why NK cells from individuals with certain KIR-ligand combinations seem better able to activate NK cell responses in the presence of specific pathogens (8)(9)(10)(11). This has been highlighted by a number of epidemiologic studies linking the generic KIR3DS/ L1 haplotypes with HIV disease progression or resistance to infection (8,9,(12)(13)(14)(15).…”

Phenotypical and functional profiles of natural killer cells exhibiting matrix metalloproteinase-mediated CD16 cleavage after anti-HIV antibody-dependent activation

“…KIR3DL/S1 generic genotyping was performed by polymerase chain reaction (PCR) using two pairs of primers specific for amplification of either KIR3DL1 or KIR3DS1 alleles, as described previously [22]. KIR3DL1 allotyping was performed by sequencing KIR3DL1 exons, as described previously [23]. Single nucleotide polymorphisms (SNP) corresponding to the KIR3DL1 alleles were identified by aligning the sequenced DNA to a reference consensus sequence consisting of KIR3DL1 cDNA sequences.…”