Immune recognition of human T-cell leukemia virus type-I (HTLV-I) by MHC-restricted cytotoxic T lymphocytes
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1Department of Immunology, School of Hygienic Sciences, Kitasato University, Kanagawa, Japan.
In our studies, it was demonstrated for the first time that HTLV-I gag and pX, and env and pX antigens are the target antigens recognized by CD8+ CTL in association with RT-1k and RT-1l class I antigens, respectively, in the rat system. Furthermore, the gag-expressing rVV and the env-expressing rVV were shown to have the potential to induce HTLV-I-specific CTL in WKA and LEW rats, respectively. These results suggest that, in general, HTLV-I structural and non-structural antigens can be recognized by CTL, and their immunogenicity for the induction of HTLV-I-specific CTL may be influenced by host MHC. Successful vaccination of mice against retrovirus tumorigenicity with the viral structural components has been demonstrated. As was the case with polyoma virus-induced tumors, utilization of rVV vectors containing HTLV-I genes for potential HTLV-I vaccines in humans may become possible if target antigens recognized by each recipient CTL can be identified prior to vaccination. Another vaccine candidate will be a synthetic peptide containing each CTL epitope. We are currently identifying the CTL epitopes, and recent results indicate that a major CTL epitope on the env-gene product is located between the env amino acids 101-112 (Tanaka et al., manuscript in preparation).
In our studies, it was demonstrated for the first time that HTLV-I gag and pX, and env and pX antigens are the target antigens recognized by CD8+ CTL in association with RT-1k and RT-1l class I antigens, respectively, in the rat system. Furthermore, the gag-expressing rVV and the env-expressing rVV were shown to have the potential to induce HTLV-I-specific CTL in WKA and LEW rats, respectively. These results suggest that, in general, HTLV-I structural and non-structural antigens can be recognized by CTL, and their immunogenicity for the induction of HTLV-I-specific CTL may be influenced by host MHC. Successful vaccination of mice against retrovirus tumorigenicity with the viral structural components has been demonstrated. As was the case with polyoma virus-induced tumors, utilization of rVV vectors containing HTLV-I genes for potential HTLV-I vaccines in humans may become possible if target antigens recognized by each recipient CTL can be identified prior to vaccination. Another vaccine candidate will be a synthetic peptide containing each CTL epitope. We are currently identifying the CTL epitopes, and recent results indicate that a major CTL epitope on the env-gene product is located between the env amino acids 101-112 (Tanaka et al., manuscript in preparation).