Epitope enhancement of a CD4 HIV epitope toward the development of the next generation HIV vaccine.
Virus-specific CD4+ T cell help and CD8+ cytotoxic T cell responses are critical for maintenance of effective immunity in chronic viral infections. The importance of CD4+ T cells has been documented in HIV infection. To investigate whether a stronger CD4+ T cell response can be induced by modifications to enhance the T1 epitope, the first CD4+ T cell epitope discovered in HIV-1-gp120, we developed a T1-specific CD4+ T cell line from a healthy volunteer immunized with a canarypox vector expressing gp120 and boosted with recombinant gp120. This T1-specific CD4+ T cell line was restricted to DR13, which is common in U.S. Caucasians and African-Americans and very frequent in Africans. Peptides with certain amino acid substitutions in key positions induced enhanced specific CD4+ T cell proliferative responses at lower peptide concentration than the original epitope. This relatively conserved CD4 epitope improved by the epitope enhancement strategy could be a component of a more effective second generation vaccine construct for HIV infection.
Okazaki
Takahiro
T
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Pendleton
C David
CD
Sarobe
Pablo
P
Thomas
Elaine K
EK
Iyengar
Sujatha
S
Harro
Clayton
C
Schwartz
David
D
Berzofsky
Jay A
JA
D016915:AIDS Vaccines / Q000737:chemistry* / Q000276:immunology*; D000409:Alanine / Q000031:analogs & derivatives / Q000276:immunology; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008969:Molecular Sequence Data
D016915:AIDS Vaccines; D018956:CD5 Antigens; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D000409:Alanine