Flynn J N, Cannon C A, Reid G, Rigby M A, Neil J C, Jarrett O
Department of Veterinary Pathology, University of Glasgow, UK.
Immunology. 1995 Jun;85(2):171-5.
Cytotoxic T-cell determinants should be an important component of a vaccine against feline immunodeficiency virus (FIV). Epitope mapping studies have revealed an immunodominant neutralization epitope within the third variable (V3) domain of the viral envelope glycoprotein comprizing 17 amino acids (residues 390-406: RAISSWKQRNRWEWRPD). We have investigated the induction of FIV-specific cytotoxicity and anti-peptide antibody in cats immunized with a multiple antigenic peptide (MAP) containing this epitope. Virus-specific lymphocytotoxicity was determined using autologous or allogeneic skin fibroblasts as target cells labelled with chromium-51 and pulsed with overlapping 10 amino acid peptides. Cytotoxic effector cells derived from fresh peripheral blood were detected in five out of 10 immunized cats. The cell-mediated immune response appeared to be directed to envelope peptide 1 (RAISSWKQRN) and peptide 2 (SWKQRNRWEW), with recognition of peptide 3 (QRNRWEWRPD) in only one cat. An antibody response to the 17 amino acid peptide immunogen was detected in seven immunized cats, which was directed to envelope peptides 2 and 3. These results suggest that different epitopes may be recognized by the cell-mediated and humoral immune responses. None of the cats was protected from challenge with the Glasgow8 isolate of FIV (FIV/GL-8). This study has implications for vaccine strategies using synthetic peptides to induce virus-specific cell-mediated immune responses.
细胞毒性T细胞决定簇应该是抗猫免疫缺陷病毒(FIV)疫苗的重要组成部分。表位作图研究揭示了病毒包膜糖蛋白第三个可变(V3)结构域内一个免疫显性中和表位,该表位由17个氨基酸组成(第390 - 406位残基:RAISSWKQRNRWEWRPD)。我们研究了用包含该表位的多抗原肽(MAP)免疫猫后FIV特异性细胞毒性和抗肽抗体的诱导情况。使用经51铬标记并用重叠的10氨基酸肽脉冲处理的自体或同种异体皮肤成纤维细胞作为靶细胞,测定病毒特异性淋巴细胞毒性。在10只免疫猫中的5只检测到了源自新鲜外周血的细胞毒性效应细胞。细胞介导的免疫反应似乎针对包膜肽1(RAISSWKQRN)和肽2(SWKQRNRWEW),仅在一只猫中检测到对肽3(QRNRWEWRPD)的识别。在7只免疫猫中检测到了对17氨基酸肽免疫原的抗体反应,该反应针对包膜肽2和3。这些结果表明,细胞介导的免疫反应和体液免疫反应可能识别不同的表位。没有一只猫能免受FIV格拉斯哥8型毒株(FIV/GL - 8)的攻击。这项研究对使用合成肽诱导病毒特异性细胞介导免疫反应的疫苗策略具有启示意义。