Immune recognition of human T-cell leukemia virus type-I (HTLV-I) by MHC-restricted cytotoxic T lymphocytes.

Y Tanaka
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Abstract

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).

mhc限制性细胞毒性T淋巴细胞对人T细胞白血病病毒i型(HTLV-I)的免疫识别
本研究首次证实HTLV-I gag和pX抗原以及env和pX抗原分别是CD8+ CTL在大鼠系统中与RT-1k和RT-1l I类抗原联合识别的靶抗原。此外,在WKA和LEW大鼠中,表达gag的rVV和表达env的rVV分别具有诱导htlv - i特异性CTL的潜力。这些结果表明,一般来说,htlv - 1结构抗原和非结构抗原都可以被CTL识别,它们诱导htlv - 1特异性CTL的免疫原性可能受到宿主MHC的影响。用病毒结构成分成功接种小鼠抗逆转录病毒致瘤性疫苗已被证实。与多瘤病毒诱导的肿瘤的情况一样,如果在接种疫苗之前能够确定每个受体CTL识别的靶抗原,则可能利用含有HTLV-I基因的rVV载体用于人类潜在的HTLV-I疫苗。另一个候选疫苗将是含有每个CTL表位的合成肽。我们目前正在鉴定CTL表位,最近的结果表明,env基因产物上的一个主要CTL表位位于env氨基酸101-112之间(Tanaka等人,手稿正在准备中)。
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