A chain section containing epitopes for cytotoxic T, B and helper T cells within a highly conserved region found in the human immunodeficiency virus type 1 Gag protein.
Cell-mediated immune responses constitute a major defense against the spread of human immunodeficiency virus type 1 (HIV-1). However, multiple alterations within a particular epitope may accumulate during disease progression, allowing the virus to escape cytotoxic T lymphocytes (CTLs). Therefore, the best candidate for a peptide vaccine that would prevent the onset of the disease might be a chain section containing epitopes for the generation of CTLs in regions of conserved sequences among different HIV-1 isolates. We previously showed that immunizing mice with synthetic peptides consisting of 23-amino acids (Gag-23mer; 287-309 amino acid residues) in a highly conserved region derived from the major core protein p24 of HIV-1 generates specific CTLs as well as antibodies. Here, we identified one CTL (T-1; 291-300) and two B-cell (B-1; 290-299 and B-2; 300-309) epitopes, all of which consisted of 10 amino acids within the region. In addition, helper T cells primed by the Gag-23mer peptide were proliferated by in vitro stimulation with a 21mer (H-1; 289-309) or a 19mer (H-2; 291-309) peptide, but not with a 17mer peptide (293-309) or 19mer peptide (287-305). Immunization with the H-1 peptide generated an antibody reactive to B-1, but not B-2, whereas that with H-2 generated an antibody reactive to B-2, but not B-1. CTLs were not generated by immunization with these peptides, indicating that the entire sequence of Gag-23mer is the helper epitope for CTLs. Thus, the Gag-23mer is a chain section containing epitopes for cytotoxic T, B and helper T-cells within a highly conserved region of HIV-1 Gag protein.
Nakamura
Y
Y
Section of Serology, Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Kameoka
M
M
Tobiume
M
M
Kaya
M
M
Ohki
K
K
Yamada
T
T
Ikuta
K
K
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000276:immunology*; D017124:Conserved Sequence; D018604:Epitope Mapping; D016655:HIV Core Protein p24 / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D016655:HIV Core Protein p24