title: HLA class II diversity in HIV-1 uninfected individuals from the placebo arm of the RV144 Thai vaccine efficacy trial.
abstract: 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.
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Baldwin
authors.forename: P K
authors.initials: PK
authors.lastname: Ehrenberg
authors.forename: A
authors.initials: A
authors.lastname: Geretz
authors.forename: H A
authors.initials: HA
authors.lastname: Prentice
authors.forename: S
authors.initials: S
authors.lastname: Nitayaphan
authors.forename: S
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.forename: J
authors.initials: J
authors.lastname: Kaewkungwal
authors.forename: P
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Connell
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Thomas
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000483:Alleles; D005787:Gene Frequency; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D059868:HLA-DP beta-Chains / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D010919:Placebos; D013785:Thailand; D016896:Treatment Outcome
chemical_list: D016915:AIDS Vaccines; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D010919:Placebos
keywords: HIV-1; HLA-DPB1; HLA-DQB1; HLA-DRB1; Human leukocyte antigen; RV144