Identification and characterization of HLA-B*5401-restricted HIV-1-Nef and Pol-specific CTL epitopes.
The identification of HIV-1 cytotoxic T lymphocyte (CTL) epitopes presented by each HLA allele and the characterization of their CTL responses are important for the study of pathogenesis of AIDS and the development of a vaccine against it. In the present study, we focused on identification and characterization of HIV-1 epitopes presented by HLA-B*5401, which is frequently found in the Asian population, because these epitopes have not yet been reported. We identified these epitopes by using 17-mer overlapping peptides derived from HIV-1 Gag, Pol, and Nef. Seven of these 17-mer peptides induced HLA-B*5401-restricted CD8+ T cell responses. Only five HLA-B*5401-restricted Pol- or Nef-specific CD8+ T cell responses were detected in the analysis using 11-mer overlapping peptides. Three Pol and two Nef optimal peptides were identified by further analysis using truncated peptides. These epitope-specific CTLs effectively killed HLA-B*5401-expressing target cells infected with HIV-1 recombinant vaccinia virus, indicating that these peptides were naturally processed by HLA-B*5401 in HIV-1-infected cells. These epitope-specific CD8+ T cells were elicited in more than 25% of chronically HIV-1-infected individuals carrying HLA-B*5401. Therefore, these epitopes should prove useful for studying the pathogenesis of AIDS in Asia and developing a vaccine against HIV-1.
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto, Japan.
Mitsutaka
M
Kitano
Naoki
N
Kobayashi
Yuka
Y
Kawashima
Tomohiro
T
Akahoshi
Kiyoshi
K
Nokihara
Shinichi
S
Oka
Masafumi
M
Takighuchi
D001208:Asia; D001402:B-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D000939:Epitopes; D015235:HLA-B Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054302:pol Gene Products, Human Immunodeficiency Virus