In vivo induction of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes and delayed-type hypersensitivity by a 23-amino acid peptide from the highly conserved region in major core protein p24.
Cell-mediated immune responses are a major immune defence mechanism against the spread of human immunodeficiency virus type 1 (HIV-1) which may lead to acquired immune deficiency syndrome (AIDS). Therefore, the best candidate for a peptide vaccine preventive from the onset of the disease might be a chain section containing both B- and T-cell epitopes in regions of conserved sequences between the different HIV-1 isolates. We previously identified the highly conserved linear B-cell epitope (23 amino acids in the major core protein p24). Since the epitopes of cytotoxic T lymphocytes (CTLs) can be defined by short synthetic peptides, we examined whether this highly conserved region can elicit viral-specific, cell-mediated immune responses. The results showed specific induction of CD8+ CTLs in mice by immunization with the Gag 13-mer peptide. Lysis of targets is specific since unpulsed cells with the same MHC haplotype or cells with a different MHC haplotype pulsed with the peptide were resistant to lysis. This in vivo response induced by the Gag 23-mer peptide was almost the same as that induced by the 15-amino acid peptide from the HIV-1 Env gp120 which is an immunodominant domain in the V3 loop. Lymphocyte proliferation of T-cell fraction from immune spleen cells was observed after in vitro stimulation with the Gag 23-mer peptide, whereas there was no apparent lymphocyte proliferation with the Env 15-mer peptide. In addition, specific antibodies were raised against Gag p24 in mice immunized with the Gag 23-mer peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Nishino
Y
Y
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Kameoka
M
M
Okada
Y
Y
Zhong
Q
Q
Kimura
T
T
Azuma
I
I
Ikuta
K
K
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D002460:Cell Line; D006168:Guinea Pigs; D016655:HIV Core Protein p24 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000209:etiology*; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016827:CD8 Antigens; D016655:HIV Core Protein p24; D010446:Peptide Fragments