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MHC Class II HLA-DR Allele Frequencies in Botswana Thumbi Ndung’u1, Simani Gaseitsiwe1, Florence Doualla-Bell1, Trevor Peter1, Enoch Sepako1, Ibou Thior1, Vladimir Novitsky2, and Max Essex2 Botswana-Harvard AIDS Institute Partnership for HIV Research and Education, Gaborone, Botswana1 and Harvard School of Public Health, Boston, USA2 Background: Botswana is a southern African country where an estimated 35% of the adult population is infected with HIV, predominantly HIV-1 subtype C. In order to facilitate HLA-based HIV-1 vaccine design and testing efforts, and to understand the role of these molecules in disease pathogenesis, we analyzed the distribution and frequencies of various HLA class II (DRB1) alleles within Botswana. Methods: DNA was extracted from blood samples obtained from 46 HIV-1 seropositive and 11 seronegative individuals who presented for blood donation at the National Blood Transfusion Center at Princess Marina Hospital, Gaborone. High resolution genotyping for the HLA-DRB was performed using sequence–specific primer PCR (SSP-PCR), followed by double strand sequencing using BigDye terminator cycle sequencing chemistry. Allele assignment was done using the Matchmaker Allele Identification software package. Results: The DRB1 allele groups DRB1*13, DRB1*15, DRB1*11, DRB1*03, and DRB1*04 were all common at high frequency in this population (22-39%), with DRB1*13 being the most commonly expressed group at 39%. Forty five of the 57 study subjects expressed at least one DRB3 allele, with 17 expressing DRB3*01, 24 expressing DRB3*02 and 18 expressing DRB3*03. All 13 individuals who were positive at the DRB4 locus expressed the DRB4*01 allele, while 14 individuals were positive for the DRB5*01 allele group. Conclusions: This is the first study to identify the most common HLA class II alleles on a population level in Botswana. Preliminary analysis shows that the frequencies and distribution of different HLA-DRB allele groups among Batswana may differ from that reported from North American and European populations. Vaccine studies that target elicitation of CD4 T-helper responses may therefore have to take account of these differences, assuming that T-helper responses are desirable in efficacious HIV-1 vaccines. Future studies may help elucidate the role that HLA-DRB polymorphisms may play in disease pathogenesis. |