สถาบันวิจัยวิทยาศาสตร์สาธารณสุข

National Institute of Health of Thailand

Authors : Kyle B. Bond*, Busarawan Sriwanthana**, Thomas W. Hodge*, Anne S. De Groot***, Timothy D. Mastro*,****, Nancy L. Young*, ****, Nattawan Promadej*, John D. Altman*****, Khanchit Limpakarnjanarat****,Janet M. McNicholl*

Affiliations:     *Centers for Disease Control and Prevention, Atlanta, Georgia 30333.

**Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000 Thailand.

***TB/HIV Research Laboratory, Brown University School of Medicine, Providence, Rhode Island 02912.

****HIV/AIDS Collaboration, Nonthaburi, 11000 Thailand.

*****Emory University, Atlanta, Georgia 30322.

           

Source:            AIDS  Research  and  Human  Retroviruses 2001; 17(8): 703-717

           

Language:       English

 

Abstract:                      

 

Only limited cytotoxic T lymphocyte (CTL) epitope mapping has been done in nonsuptype B HIV-infected persons. We used molecular immunogenetic tools to determine HIV-specific CTL responses in HIV-1 Env suptype E-infected female sex workers ( FSWs) from northern Thailand, where more than 50% of the population is HLA-A11 positive. EpiMatrix, a computer-based T cell epitope prediction algorithm, and a manual editing approach were used to predict 77 possible HLA-A11 CTL epitopes in HIV-1,some of which were conserved between suptypes B and E. MHC binding of these peptides was determined in an HLA-A11 stabilization assay, and binding peptides were tested for CTL recognition in eight HLA-A11-positive FSWs. Suptype E versions of know HLA-A2 suptype B HIV epitopes were also tested in four HLA-A2 positive FSWs. CTL responses were detected in all HLA-A11-positive and in three of four HLA-A2-positive persons. Among the 12 FSWs responses to peptide were found to Pol in 9 (75%), Env in 7(58%),Nef in 5 (42%) ,and Gag in 5(42%),and to conserved epitopes in 8 (67%). To identify HLA-A11 CTL epitopes in the absence of prediction tools, it would have been necessary to test almost 3000 10-mer peptides. EpiMatrix and manual prediction reduced this number to 77, of which 26 were MHC binding and 12 were CTL epitopes.Six of these HLA-A11 CTL epitopes have not been previously reported and are located in RT, gp120, and gp41. This report of CTL responses in suptype E-infected individuals defines epitopes that may be useful in HIV pathogenesis or vaccine studies.