Cytolytic T lymphocytes (CTLs) from HIV-1 subtype C-infected Indian patients recognize CTL epitopes from a conserved immunodominant region of HIV-1 Gag and Nef.
Analysis of the human immunodeficiency virus type 1 (HIV-1) cytolytic T lymphocyte (CTL) epitopes recognized by the targeted population is critical for HIV-1 vaccine design. Peripheral blood mononuclear cells from 47 Indian subjects at different stages of HIV-1 infection were tested for HIV-1 Gag-, Nef-, and Env-specific T cell responses by interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay, using pools of overlapping peptides. The Gag and Nef antigens were targeted by 83% and 36% of responders. Five immunodominant regions, 4 in Gag and 1 in Nef, were identified in the study; these regions are conserved across clades, including the African subtype C clade. Three antigenic regions were also found to be recognized by CTLs of the study participants. These regions were not identified as immunodominant regions in studies performed in Africa, which highlights the importance of differential clustering of responses within HIV-1 subtype C. Twenty-six putative epitopes--15 Gag (10 in p24 and 5 in p17), 10 Nef, and 1 Env (gp 41)--were predicted using a combination of peptide matrix ELISPOT assay and CTL epitope-prediction software. Ninety percent of the predicted epitopes were clustered in the conserved immunodominant regions of the Gag and Nef antigens. Of 26 predicted epitopes, 8 were promiscuous, 3 of which were highly conserved across clades. Three Gag and 4 Nef epitopes were novel. The identification of conserved epitopes will be important in the planning of an HIV-1 vaccine strategy for subtype C-affected regions.
Thakar
Madhuri R
MR
National AIDS Research Institute, Bhosari, Pune, India. mthakar@nariindia.org
Bhonge
Leena S
LS
Lakhashe
Samir K
SK
Shankarkumar
U
U
Sane
Suvarna S
SS
Kulkarni
Smita S
SS
Mahajan
Bharati A
BA
Paranjape
Ramesh S
RS
D016915:AIDS Vaccines / Q000276:immunology; D000328:Adult; D000595:Amino Acid Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D015693:Gene Products, nef / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007194:India; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015683:Gene Products, gag; D015693:Gene Products, nef; D016056:Immunodominant Epitopes; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma