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

• Published in: Tissue antigens 2015-02, Vol.85 (2), p.117-126
• Main Authors: Baldwin, K. M., Ehrenberg, P. K., Geretz, A., Prentice, H. A., Nitayaphan, S., Rerks-Ngarm, S., Kaewkungwal, J., Pitisuttithum, P., O'Connell, R. J., Kim, J. H., Thomas, R.
• Format: Article
• Language: English
• Subjects: AIDS Vaccines - immunology; Alleles; Gene Frequency; Genetic Variation; Haplotypes - genetics; Histocompatibility Antigens Class II - genetics; HIV Infections - genetics; HIV Infections - immunology; HIV-1; HIV-1 - immunology; HLA-DP beta-Chains - genetics; HLA-DPB1; HLA-DQ beta-Chains - genetics; HLA-DQB1; HLA-DRB1; HLA-DRB1 Chains - genetics; Human immunodeficiency virus; Human immunodeficiency virus 1; Human leukocyte antigen; Humans; Placebos; RV144; Thailand; Treatment Outcome
• ISSN: 0001-2815; 1399-0039; 1399-0039
• DOI: 10.1111/tan.12507

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 DRB1*07:01, DRB1*09:01, DRB1*12:02, DRB1*15:02, DQB1*02:01/02, DQB1*03:01, DQB1*03:03, DQB1*05:01, DQB1*05:02, DPB1*04:01:01, DPB1*05:01:01, and DPB1*13:01:01. We identified 28 rare alleles with frequencies of less than 1% in the Thai individuals. Ambiguity for HLA‐DPB1*28:01 in exon 2 was resolved to DPB1*296:01 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.