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70 HIV-1 Gag, Pol Cross-Clade-Specific Cytotoxic T Lymphocytes and gag Epitope Mapping in Asymptomatic HIV-1-Infected Thai Patients
S. Buranapraditkun*1,2, K. Ruxrungtham1,2, P. Hansasutha1,3, S. Rowland-Jones3, S. Sirivichaykul1,2, P. Warachit 4, M. Honda5, and P. Phanuphak1,2
1Chulalongkorn Univ., BKK; 2Thai Red Cross AIDS Res. Ctr., BKK; 3John Radcliffe Hosp., Oxford, UK; 4Dept. of Med. Sci., Thailand; and 5Natl. Inst. of Infectious Diseases, Tokyo, Japan
Background: Our previous study, using Cr51 release classic CTL assay, has shown that HIV-1 gag is the most common antigen recognized by >90% of Thai patients infected by HIV-1 clade A/E. In addition, HIV-1 gag has a very high rate of cross-clade CTL activity between clade A and B among clade A/E-infected Thai patients. The HLA polymorphism among Thais is also remarkably different from the western cohorts. Further study in HIV-gag epitope mapping in HIV-infected Thai patients is warranted.
Methods: Both the CTL epitope mapping and HLA restriction were performed by Cr51 release classic CTL assay. HIV-1 clade A gag-truncated peptides (a.a. 1-499; consensus sequence of 92UG037; each is 20 a.a. in length with 10-a.a. overlaps between sequential peptides) were used for gag-CTL epitope mapping (kindly provided from NIH AIDS Research and Reference Reagent Program, USA). HLA class I was analyzed by genotyping.
Results: Ten patients (mean CD4 count 535 cells/mm3; median plasma HIV-RNA 7,502 copies/ml) with gag-specific CTL were studies for epitope mapping. Fourteen gag-specific epitopes were identified: 7 in p17 and 7 in the p24 region. Of note, 40% of the patients recognized the same epitope: p24 peptide 275(282. In the HLA restriction study, A2 (p24, 141(160), A26 (p24, 167(175), B7 (p24, 181(191), and C1 (p24, 275(282; 4 cases) restriction gag epitopes were identified. Interestingly, the C1- or Cw1-restricted gag epitope is the most common epitope found in this cohort and has not been reported in the literature.
Conclusions: Fourteen HIV-1 gag-specific epitopes were identified among 10 patients infected with clade A/E. P24 epitope 272(282 with C1 or Cw1 restriction is the most common epitope found in this cohort. Further study is required in a larger sample size to find the common and immunodominant epitopes among Thai patients.
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