Kurata A, Palker T J, Streilein R D, Scearce R M, Haynes B F, Berzofsky J A
Molecular Immunogenetics and Vaccine Research Section, National Cancer Institute, Bethesda, MD 20892.
J Immunol. 1989 Sep 15;143(6):2024-30.
HTLV-I (human T cell lymphotropic virus type 1) is the retrovirus causally related to adult T cell leukemia/lymphoma and is also associated with a neurological disorder, tropical spastic paraparesis, or HTLV-I-associated myelopathy. The development of these two different diseases among HTLV-I-infected individuals may depend in part on differences in their T cell immunity associated with a difference of HLA phenotype. Peptides corresponding to 17 sites in the HTLV-I envelope protein were tested for their antigenicity for lymph node cells from B10.BR, B10.D2, B10.A(5R), and B10.HTT congenic mice, representing four independent MHC haplotypes, immunized with the native envelope protein. Ten of the 17 tested sites were predicted to be amphipathic alpha-helical sites and all of them were found to be antigenic for at least one of the four MHC congenic strains of mice. Three of the 17 sites were amphipathic 3(10)-helical sites and four sites were predicted to be non-helical sites: none of the 3(10)-helical sites were antigenic and only one of four non-predicted sites was found to be immunodominant. Furthermore, three potent immunodominant peptides, V1E1 (342-363), V1E8/SP4a (191-209), and V1E10 (141-156) were also shown to be immunogenic; i.e., these peptides could be used to immunize mice to elicit proliferative responses of lymph node cells to the native HTLV-I envelope protein. Furthermore, these three peptides were able to prime animals for an enhanced antibody response to the native protein. Because this priming followed the same Ir gene control as the proliferative response, it probably reflects the ability of these peptides to prime helper T cells. The localization of immunodominant sites in HTLV-I envelope protein in mice may be useful for finding antigenic and immunogenic sites in humans, for developing a peptide vaccine for the virus, and possibly for aiding in prognosis for the development of different disease manifestations of HTLV-I infection.
人类嗜T淋巴细胞病毒1型（HTLV-I）是一种逆转录病毒，与成人T细胞白血病/淋巴瘤有因果关系，还与一种神经系统疾病——热带痉挛性截瘫或HTLV-I相关脊髓病有关。在HTLV-I感染个体中这两种不同疾病的发生可能部分取决于与HLA表型差异相关的T细胞免疫差异。对来自代表四种独立MHC单倍型的B10.BR、B10.D2、B10.A(5R)和B10.HTT同源小鼠的淋巴结细胞，检测了与HTLV-I包膜蛋白中17个位点对应的肽对用天然包膜蛋白免疫后的抗原性。17个检测位点中的10个被预测为两亲性α螺旋位点，并且发现它们对四种MHC同源小鼠品系中的至少一种具有抗原性。17个位点中的3个是两亲性3(10)-螺旋位点，4个位点被预测为非螺旋位点：3(10)-螺旋位点均无抗原性，4个非预测位点中只有1个被发现是免疫显性的。此外，三种强效免疫显性肽，V1E1（342-363）、V1E8/SP4a（191-209）和V1E10（141-156）也显示出具有免疫原性；即这些肽可用于免疫小鼠以引发淋巴结细胞对天然HTLV-I包膜蛋白的增殖反应。此外，这三种肽能够使动物对天然蛋白产生增强的抗体反应。由于这种启动遵循与增殖反应相同的Ir基因控制，它可能反映了这些肽启动辅助性T细胞的能力。小鼠中HTLV-I包膜蛋白免疫显性位点的定位可能有助于在人类中找到抗原性和免疫原性位点、开发针对该病毒的肽疫苗，并且可能有助于预测HTLV-I感染不同疾病表现的发展。
