Human immunodeficiency virus type 1 Nef epitopes recognized in HLA-A2 transgenic mice in response to DNA and peptide immunization.
We investigated the immune response against a human immunodeficiency virus type 1 (HIV-1) nef DNA sequence administered epidermally in mice transgenic for the human major histocompatibility complex (MHC) class I molecule HLA-A201. Ten potential HLA-A2 binding 9-mer Nef peptides were identified by a computer-based search algorithm. By a cell surface MHC class I stabilization assay, four peptides were scored as good binders, whereas two peptides bound weakly to HLA-A2. After DNA immunization, cytotoxic T lymphocyte (CTL) responses were predominantly directed against the Nef 44-52, 81-89, and 85-93 peptides. Interestingly, the 44-52 epitope resides outside the regions of Nef where previously described CTL epitopes are clustered. Dominance among Nef-derived peptides did not strictly correlate with HLA-A2 binding, in that only one of the high-affinity binding peptides was targeted in the CTL response. The 44-52, 85-93, and 139-147 peptides also generated specific CTLs in response to peptide immunization. T helper cell proliferation was detected after stimulation with 20-mer peptides in vitro. Three Nef regions (16-35, 106-125, and 166-185) dominated the T helper cell proliferation. The implications of these results for the development of DNA-based vaccines against HIV is discussed.
Sandberg
J K
JK
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, 171 77, Sweden. jsandber@adarc.adarc.org
Leandersson
A C
AC
Devito
C
C
Kohleisen
B
B
Erfle
V
V
Achour
A
A
Levi
M
M
Schwartz
S
S
Kärre
K
K
Wahren
B
B
Hinkula
J
J
D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015488:HIV Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte; D015693:Gene Products, nef; D015488:HIV Antigens; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D054311:nef Gene Products, Human Immunodeficiency Virus