Primary induction of human cytotoxic lymphocytes against a synthetic peptide of the human immunodeficiency virus type 1 protease.
Identification of in vitro immunogenic T-cell epitopes is important for the design of immunotherapeutics targeted to specific antigenic sites. To identify candidate cytotoxic T-lymphocyte (CTL) epitopes in the protease of human immunodeficiency virus type 1 (HIV-1) strain MN, we synthesized 9-mer and 10-mer peptides containing the HLA-A*0201 binding motif. Binding affinity of the peptides was measured by HLA-A*0201 up-regulation on T2 cells. Peptides with high binding-affinity were tested for their ability to stimulate primary CTLs from healthy HIV-negative blood donors. Peptide-specific CTLs were obtained from five out of six donors by stimulation with a 9-mer (LVGPTPVNI) or a 10-mer (VLVGPTPVNI) peptide derived from a highly conserved amino acid stretch in the C-terminal region of the protease. Addition of peptide-specific CTLs to acutely HIV-infected lymphocytes resulted in inhibition of p24gag production. In conclusion, a highly conserved HIV protease peptide regularly elicits peptide-specific CTLs. Targeting immune responses against defined epitopes in non-variable regions may be a feasible way to minimize the risk of virus escape from immune surveillance.
Kónya
J
J
Karolinska Institute, Microbiology and Tumorbiology Center, Stockholm, Sweden.
Stuber
G
G
Björndal
A
A
Fenyö
E M
EM
Dillner
J
J
D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000032:analysis*; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D016333:HIV Protease / Q000276:immunology*; D015497:HIV-1 / Q000201:enzymology* / Q000276:immunology; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D016655:HIV Core Protein p24; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D016333:HIV Protease