Kast W M, Boog C J, Roep B O, Voordouw A C, Melief C J
Division of Immunology, Netherlands Cancer Institute, Amsterdam.
J Immunol. 1988 May 1;140(9):3186-93.
C57BL/6 (B6, H-2b) mice are CTL responders to both Sendai virus and Moloney leukemia virus. In the former response the H-2Kb class I MHC molecule is used as CTL restriction element, in the latter response the H-2Db molecule. B6 dendritic cells (DC) are superior in the presentation of Sendai virus Ag to CTL in comparison with B6 normal spleen cells. Con A blasts have even less capacity to present viral Ag than NSC, and LPS blasts show an intermediate capacity to present viral Ag. H-2Kb mutant bm1 mice do not generate a CTL response to Sendai virus, but respond to Moloney leukemia virus, as demonstrated by undetectable CTL precursors to Sendai virus and a normal CTL precursor frequency to Moloney virus. Compared to B6 mice, other H-2Kb mutant mice show decreased Sendai virus-specific CTL precursor frequencies in a hierarchy reflecting the response in bulk culture. The Sendai virus-specific CTL response defect of bm1 mice was not restored by highly potent Sendai virus-infected DC as APC for in vivo priming and/or in vitro restimulation. In mirror image to H-2Kb mutant bm1 mice, H-2Db mutant bm14 mice do not generate a CTL response to Moloney virus, but respond normally to Sendai virus. This specific CTL response defect was restored by syngeneic Moloney virus-infected DC for in vitro restimulation. This response was Kb restricted indicating that the Dbm14 molecule remained largely defective and that a dormant Kb repertoire was aroused after optimal Ag presentation by DC. In conclusion, DC very effectively present viral Ag to CTL. However, their capacity to restore MHC class I determined specific CTL response defects probably requires at least some ability of a particular MHC class I/virus combination to associate and thus form an immunogenic complex.
C57BL/6（B6，H-2b）小鼠对仙台病毒和莫洛尼白血病病毒均为细胞毒性T淋巴细胞（CTL）应答者。在前一种应答中，H-2Kb I类主要组织相容性复合体（MHC）分子用作CTL限制元件，在后一种应答中则是H-2Db分子。与B6正常脾细胞相比，B6树突状细胞（DC）在向CTL呈递仙台病毒抗原方面更具优势。刀豆蛋白A刺激的母细胞呈递病毒抗原的能力甚至比正常脾细胞更低，而脂多糖刺激的母细胞呈递病毒抗原的能力处于中等水平。H-2Kb突变体bm1小鼠对仙台病毒不产生CTL应答，但对莫洛尼白血病病毒有应答，这表现为对仙台病毒检测不到CTL前体细胞，而对莫洛尼病毒的CTL前体细胞频率正常。与B6小鼠相比，其他H-2Kb突变小鼠的仙台病毒特异性CTL前体细胞频率降低，并呈现出一种反映大量培养中应答情况的等级关系。用高效感染仙台病毒的DC作为抗原呈递细胞（APC）进行体内致敏和/或体外再刺激，未能恢复bm1小鼠的仙台病毒特异性CTL应答缺陷。与H-2Kb突变体bm1小鼠情况相反，H-2Db突变体bm14小鼠对莫洛尼病毒不产生CTL应答，但对仙台病毒的应答正常。通过同基因感染莫洛尼病毒的DC进行体外再刺激，可恢复这种特异性CTL应答缺陷。这种应答受Kb限制表明Dbm14分子在很大程度上仍然存在缺陷，并且在DC进行最佳抗原呈递后，休眠的Kb库被激活。总之，DC能非常有效地将病毒抗原呈递给CTL。然而，它们恢复由I类MHC决定的特异性CTL应答缺陷的能力，可能至少需要特定的I类MHC/病毒组合有一定的结合能力，从而形成免疫原性复合物。
