HLA class II diversity in HIV-1 uninfected individuals from the placebo arm of the RV144 Thai vaccine efficacy trial.

The RV144 HIV vaccine trial in Thailand elicited antibody responses to the envelope of HIV-1, which correlated significantly with the risk of HIV-1 acquisition. Human leukocyte antigen (HLA) class II molecules are essential in antigen presentation to CD4 T cells for activation of B cells to produce antibodies. We genotyped the classical HLA-DRB1, DQB1, and DPB1 genes in 450 individuals from the placebo arm of the RV144 study to determine the background allele and haplotype frequencies of these genes in this cohort. High-resolution 4 and 6-digit class II HLA typing data was generated using sequencing-based methods. The observed diversity for the HLA loci was 33 HLA-DRB1, 15 HLA-DQB1, and 26 HLA-DPB1 alleles. Common alleles with frequencies greater than 10% were DRB107:01, DRB109:01, DRB112:02, DRB115:02, DQB102:01/02, DQB103:01, DQB103:03, DQB105:01, DQB105:02, DPB104:01:01, DPB105:01:01, and DPB113:01:01. We identified 28 rare alleles with frequencies of less than 1% in the Thai individuals. Ambiguity for HLA-DPB128:01 in exon 2 was resolved to DPB1296:01 by next-generation sequencing of all exons. Multi-locus haplotypes including HLA class I and II loci were reported in this study. This is the first comprehensive report of allele and haplotype frequencies of all three HLA class II genes from a Thai population. A high-resolution genotyping method such as next-generation sequencing avoids missing rare alleles and resolves ambiguous calls. The HLA class II genotyping data generated in this study will be beneficial not only for future disease association/vaccine efficacy studies related to the RV144 study, but also for similar studies in other diseases in the Thai population, as well as population genetics and transplantation studies.