Uenishi H, Iwanami N, Kuribayashi K, Tamamura H, Fujii N, Nakatani T, Kawasaki T, Yamagishi H
Department of Biophysics, Graduate School of Science, Kyoto University, Japan.
Immunol Lett. 1998 May;62(1):33-8. doi: 10.1016/s0165-2478(98)00020-0.
The leader signal sequence of the non-structural gag-encoded glycoprotein precursor, Pr75gag, of Friend murine leukemia virus (F-MuLV) contains overlapping epitopes, SIVLCCLCL (p71-79) and CCLCLTVFL (p75 83) that activate Friend virus (FV)-induced tumor (FBL-3)-specific cytotoxic T-lymphocytes (CTL) (Kondo et al., J. Virol., 69, 1995, 6735-6741; Chen et al., J. Virol., 70, 1996, 7773-7782). It was investigated whether these two peptides are recognized by a single CTL clone or by individual clones with different specificities. The results show that both hydrophobic and cysteine-containing peptides are bound to H-2Db class I major histocompatibility complex (MHC) molecules and cross-recognized by a single CTL clone as well as bulk-cultured CTL from the spleens of mice immunized with FBL-3. The peptide p71-79 was effective for sensitizing target cells to lysis by CTL in the concentration of common antigenic peptides. Moreover, peptide p75-83 was 1000-fold more potent than the peptide p71-79. Specific cytotoxicity assays with variant peptides with alanine- and serine-substitutions suggested a highly complex function of the disulfide bond-forming peptides potentially sensitive to small sequence differences. The dominance of CTL responses to the transmembrane region is discussed in light of the high affinity of a novel hydrophobic peptide to compete with other peptides for binding to MHC molecules.
弗氏小鼠白血病病毒（F-MuLV）的非结构gag编码糖蛋白前体Pr75gag的前导信号序列包含重叠表位SIVLCCLCL（p71 - 79）和CCLCLTVFL（p75 - 83），这些表位可激活弗氏病毒（FV）诱导的肿瘤（FBL-3）特异性细胞毒性T淋巴细胞（CTL）（近藤等人，《病毒学杂志》，69，1995，6735 - 6741；陈等人，《病毒学杂志》，70，1996，7773 - 7782）。研究了这两种肽是被单个CTL克隆识别，还是被具有不同特异性的单个克隆识别。结果表明，含疏水氨基酸和含半胱氨酸的肽均与H-2Db I类主要组织相容性复合体（MHC）分子结合，并被单个CTL克隆以及来自用FBL-3免疫的小鼠脾脏的大量培养CTL交叉识别。在常见抗原肽浓度下，肽p71 - 79能有效使靶细胞对CTL裂解敏感。此外，肽p75 - 83的效力比肽p71 - 79高1000倍。用丙氨酸和丝氨酸取代的变体肽进行的特异性细胞毒性试验表明，形成二硫键的肽的功能高度复杂，可能对小的序列差异敏感。鉴于一种新型疏水肽具有高亲和力，能与其他肽竞争结合MHC分子，讨论了CTL对跨膜区反应的优势。
