CRF01_AE (subtype E) Gag specific T-lymphocyte responses in untreated HIV-infected and exposed but uninfected Thais.
Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10285)
Sriwanthana B, Jitjuk B, Wichukchinda N, Rojanawiwat A, Tanaka M, Pathipvanich P, Ariyoshi K, Sawanpanyalert P National Institute of Health, Nonthaburi, Thailand
Background : Identification of HIV-1 Cytotoxic T lymphocyte (CTL) epitopes is essential for the design and evaluation of candidate HIV preventive/therapeutic vaccines in Thailand, where host genetic backgrounds and strains of circulating HIV-1 are different from those in other parts of the world. Methods : Fifty untreated HIV-infected individuals with a relatively high CD4 count of over 200/mul and a plasma viral load ranging from<1,000 to 600,000 RNA copies /ml, and 19 exposed but uninfected (EU) individuals were recruited from the Lampang HIV Couple Cohort from August to December 2003. PBMCs were examined for HIV-1 Gag specific T-lymphocyte interferon gamma production in an enzyme-linked immunospot assay (ELISpot) using 10 amino-acid overlapping 15-mer peptides of the most common CRF01_AE Gag sequences within the cohort. Ten peptides were pooled in a Matrix way. Responses with 4 times over the background were considered positive. Results : Cellular responses to one or more Gag peptides were detected in 33 of 50 (66%) infected persons and 5 of 19 (26%) EU. Twenty-four (72.7%) of 33 infected persons with a significant response, recognized multiple peptides whereas 3 of 5 EU with a significant response, recognized a single peptide. There was no significant association between the pattern of CTL recognitions and viral load. Using the Matrix approach, we identified 6 different peptides (3 among infected and 3 among EU persons), of which 5 peptides potentially convey a new CRF01_AE Gag E CTL epitope. Intriguingly, EU recognized peptides that were rarely recognised by infected persons; two peptides recognized by our EU persons coincidently convey CTL epitopes (KRWIILGLNK, IILGLNKIVR) that were recognized by EU persons in Africa. Conclusion : Our results confirm that cellular responses specific to CRF01_AE Gag exist in both HIV-infected and exposed uninfected individuals. The pattern of CTL recognition among EU may differ from that in infected persons.
Keywords: AEGIS, Acquired Immunodeficiency Syndrome, Genes, gag, HIV Seropositivity, T-Lymphocytes, HIV-1, T-Lymphocytes, Cytotoxic, Epitopes, Thailand, CD4 Lymphocyte Count, Africa, genetics, immunology
