An HLA-directed molecular and bioinformatics approach identifies new HLA-A11 HIV-1 subtype E cytotoxic T lymphocyte epitopes in HIV-1-infected Thais.
Only limited cytotoxic T lymphocyte (CTL) epitope mapping has been done in nonsubtype B HIV-infected persons. We used molecular immunogenetic tools to determine HIV-specific CTL responses in HIV-1 Env subtype 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 subtypes 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. Subtype E versions of known HLA-A2 subtype 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 peptides 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 predictions 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 subtype E-infected individuals defines epitopes that may be useful in HIV pathogenesis or vaccine studies.
Bond
K B
KB
Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Sriwanthana
B
B
Hodge
T W
TW
De Groot
A S
AS
Mastro
T D
TD
Young
N L
NL
Promadej
N
N
Altman
J D
JD
Limpakarnjanarat
K
K
McNicholl
J M
JM
D000465:Algorithms; D015331:Cohort Studies; D003601:Cytotoxicity Tests, Immunologic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000276:immunology; D005260:Female; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D059870:HLA-A11 Antigen; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis / Q000276:immunology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011477:Sex Work; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013785:Thailand; D014764:Viral Proteins / Q000138:chemical synthesis / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015683:Gene Products, gag; D015693:Gene Products, nef; D015684:Gene Products, pol; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D014764:Viral Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus