Among all human T-cell leukemia virus type 1 proteins, tax, polymerase, and envelope proteins are predicted as preferential targets for the HLA-A2-restricted cytotoxic T-cell response

Abstract

The human T-cell leukemia virus type 1 (HTLV-1) is a human retrovirus associated with two diseases for which no successful treatment is yet available; the development of a vaccine is therefore an important issue. Since HTLV-1 is a persistent virus, an efficient vaccine will probably require a cytotoxic T-lymphocyte (CTL) response in addition to the production of antibodies. To identify potential CTL epitopes, we have selected, within all of the HTLV-1 proteins, nonapeptides containing anchor residues required for association with HLA-A2 molecules (residues at positions 2 and 9), which is the most frequently occurring A allele in all human populations. A set of 111 peptides was synthetized and tested in vitro in two assembly assays using processingdefective T2 cells. Anchor motifs selected were those containing two major anchor residues (L 2 /M 2 /I 2 -V 9 /L 9 /I 9 ) (one letter amino-acid code) and those including tolerated anchor residues (V 2 /A 2 /T 2 and/or A 9 /M 9 /T 9 ). The analysis of the binding capacity of the peptides confirms the high efficiency of the L 2 -V 9 anchor motif and shows that a systematic research of potential binding peptides should exclude peptides containing known detrimental residues rather than select only peptides with known favored residues. We show that 39 peptides representative of all the HTLV-1 proteins are able to bind to HLA-A2 molecules. Strong binder peptides which are very likely good CTL epitopes were identified in three HTLV-1 proteins, Tax, envelope, and polymerase. Three of the strong binder peptides correspond to previously described HLA-A2-restricted CTL epitopes in the Tax protein, and two others are localized in a domain of the viral envelope recognized by natural neutralizing antibodies. This latter result has important implications for the development of an anti-HTLV-1 vaccine.

Evidence for the Chronic in Vivo Production of Human T Cell Leukemia Virus Type I Rof and Tof Proteins from Cytotoxic T Lymphocytes Directed against Viral Peptides

“…The CTL response to the Tof 156–164, Rof 31–38, and Rof 57–65 peptides is in good agreement with our previous finding that these peptides bind to HLA-A2 molecules in vitro 9. We also found that the Rof 38–46 and the Tof 31–39 peptides act as HLA-A2–restricted epitopes, although they were not previously considered as HLA-A2 binders.…”

“…1 B) and another in the pX-II protein (Tof 156–164; Fig. 1 C) were able to associate to HLA-A2 molecules in vitro 9. We have now examined whether CTLs directed against these peptides were detected in HLA-A2 HTLV-I–infected individuals.…”

“…1B and Fig. C) have been described previously 9. Tax, pX-I, and pX-II peptides were synthesized with the PepSet synthesis system (Chiron Mimotopes), suspended in water at 2 mM, and stored at −20°C.…”

Identification in humans of HPV-16 E6 and E7 protein epitopes recognized by cytolytic T lymphocytes in association with HLA-B18 and determination of the HLA-B18-specific binding motif

“…g in 50 ? l) were incubated with exogenous peptides in Eppendorf microtubes for 24 h at 4°C [31]. In the standard asay, peptides were screened at 0.1 and 10 ?…”

Mapping the molecular characteristics of Brazilian human T-cell lymphotropic virus type 1 Env (gp46) and Pol amino acid sequences for vaccine design

“…Multiple neutralizing monoclonal antibodies to linear epitopes within amino acids 175-200 of the gp46 and more rarely to epitopes into the carboxy terminal of the protein have been described using immunoreactive assays (Baba et al 1993). The antiviral cytotoxic T-lymphocyte (CTL) is activated in vivo and directed mainly to the HTLV-1 Tax regulatory protein and to a lesser extent to the structural Gag, Env, and Pol proteins (Kannagi et al 1991, Parker et al 1992, Elovaara et al 1993, Pique et al 1996.…”