Effective recognition of HIV-1-infected cells by HIV-1 integrase-specific HLA-B∗4002-restricted T cells.
HLA-B∗4002 is one of the common HLA-B alleles in the world. All 7 reported HLA-B∗4002-restricted HIV epitopes are derived from Gag, Nef, and Vpr. In the present study we sought to identify novel HLA-B∗4002-restricted HIV epitopes by using overlapping 11-mer peptides of HIV-1 Nef, Gag, and Pol, and found that 6 of these 11-mer Pol peptides included HLA-B∗4002-restricted epitopes. Analysis using truncated peptides of these 6 peptides defined 4 optimal Pol (integrase) epitopes. All epitopes previously reported had Glu at position 2 (P2), suggesting that Glu at P2 is the anchor residue for HLA-B∗4002; whereas only 2 of the integrase epitopes that we here identified had Glu at P2. CTL clones specific for the 2 epitopes effectively recognized HIV-1-infected cells whereas those for other 2 epitopes only weakly recognized them. The antigen sensitivity of the former clones for the epitope peptide was much higher than that of the latter clones, suggesting 2 possibilities: 1) the former T cells have high-affinity TCRs and/or 2) the epitope peptides recognized by the former T cells are highly presented by HLA-B∗4002 in HIV-1-infected cells. These integrase-specific T cells with high antigen sensitivity may contribute to the suppression of HIV-1 replication in HIV-1-infected HLA-B∗4002+ individuals.
Watanabe
Tamayo
T
Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Murakoshi
Hayato
H
Gatanaga
Hiroyuki
H
Koyanagi
Madoka
M
Oka
Shinichi
S
Takiguchi
Masafumi
M
D000956:Antigens, Viral / Q000276:immunology; D002461:Cell Line, Transformed; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D019427:HIV Integrase / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1