BALB/c-H-2dm2 mice (H-2KdI-AdI-EdDd), a congenic strain of BALB/c mice, have a deletion of the class I MHC Ag, H-2Ld. This gene encodes the exclusive class I MHC-restricting gene product for vesicular stomatitis virus-specific cytolytic T lymphocytes. When dm2 mice were immunized with infectious vesicular stomatitis virus, a specific CTL response was generated. These CTL lysed VSV-infected targets that expressed Iad gene products, but not VSV-infected Iad- targets. The CTL were used initially as long term cytolytic lines; 13 CTL clones were derived by limit dilution. All of the clones expressed the phenotype CD3+, CD4+, CD8-; some clones expressed TCR that are members of the V beta 8 family, others did not. The clones were restricted by class II MHC Ag, both I-Ad and I-Ed serving as restricting elements for individual clones of the panel. All of the clones derived from dm2 mice were specific for the immunizing serotype, Indiana, of VSV and did not lyse syngeneic cells infected with VSV of the New Jersey serotype. Studies using defective interfering virus particles, UV light-inactivated virus, and purified micelles of the viral glycoprotein indicated that infectious virus was not required for sensitization of target cells for immune recognition by the class II MHC-restricted CTL clones. Additional studies using recombinant vaccinia virus vectors to sensitize targets confirmed the specificity of the clones for the viral glycoprotein. These studies also demonstrated a cryptic population of class II-restricted CTL in BALB/c lines specific for VSV G. Naturally occurring variant viruses and mutant viruses, selected for escape from neutralization by mAb, were used in an effort to map the determinant(s) recognized; on the basis of patterns of target cell lysis, three groups of epitopes recognized by the clones were defined. Therefore, in the absence of the class I MHC Ag required for a CTL response to VSV, dm2 mice generated CTL with the CD4+ phenotype that recognized different epitopes on the viral glycoprotein, and lysed cells in a class II-MHC restricted, Ag-specific manner.

译文

BALB/c-H-2dm2小鼠 (H-2KdI-AdI-EdDd) 是BALB/c小鼠的同系菌株,H-2Ld具有I类MHC Ag的缺失。该基因编码水泡性口炎病毒特异性溶细胞T淋巴细胞的唯一I类MHC限制基因产物。当用传染性水泡性口炎病毒免疫dm2小鼠时,会产生特定的CTL反应。这些CTL裂解了表达Iad基因产物的VSV感染的靶标,但不表达VSV感染的Iad靶标。CTL最初用作长期溶细胞系; 通过极限稀释获得13个CTL克隆。所有克隆均表达表型CD3,CD4,CD8-; 一些克隆表达了vβ8家族成员的TCR,而其他克隆则没有。克隆受到II类MHC Ag的限制,i-ad和i-ed均作为面板各个克隆的限制元素。来自dm2小鼠的所有克隆均对VSV的免疫血清型印第安纳州具有特异性,并且不会裂解被新泽西州血清型VSV感染的同系细胞。使用有缺陷的干扰病毒颗粒,紫外线灭活病毒和病毒糖蛋白的纯化胶束进行的研究表明,感染性病毒不需要II类MHC限制性CTL克隆对靶细胞进行免疫识别的敏化。使用重组痘苗病毒载体对靶标敏感的其他研究证实了克隆对病毒糖蛋白的特异性。这些研究还表明,在针对VSV G的BALB/c品系中,具有II类限制性CTL的隐秘群体。天然存在的变异病毒和突变病毒被选择用于逃避mAb的中和,以试图绘制确定的决定因素; 根据靶细胞裂解的模式,定义了克隆识别的三组表位。因此,在缺乏对VSV的CTL应答所需的I类mhcag的情况下,dm2小鼠产生了具有CD4表型的CTL,该表型识别了病毒糖蛋白上的不同表位,并以II类MHC受限的Ag-特异性方式裂解了细胞。

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