Vidard L, Rock K L, Benacerraf B
Institut Curie Unite d'Immunogenetique CNRS URA 1413 75231 Paris, France.
J Immunol. 1991 Sep 15;147(6):1786-91.
The ability of splenic APC and a B cell hybridoma (LS.102.9) to process and present OVA to a panel of T-T hybridomas with different fine specificities was investigated. Splenic APC process and present OVA to all the T-T hybrids. The B cell hybridoma could similarly process and present OVA to some T-T hybrids but was very inefficient in stimulating two of the T cell hybridomas. The presentation of native OVA to these two T-T hybrids was significantly increased by leupeptin. Pulsing experiments demonstrated that leupeptin acted on the APC at a step before the processed Ag was displayed on the cell surface in association with MHC molecules. Leupeptin has no effect on the presentation of OVA peptides by LS.102.9 to the T-T hybrids. Leupeptin inhibits the generation of the epitopes of OVA that LS.102.9 produces under basal conditions. We also surveyed the effect of other protease inhibitors and observed similar augmenting and inhibitory effects on the presentation of selected OVA epitopes. The augmentation of processing by a protease inhibitor indicates that in the lysosomal/endosomal compartment proteases have capacity to both generate and destroy immunogenic peptides. Our data suggest that protease inhibitors could potentially be used as immunomodulators and are discussed in terms of physiology of the lysosomal/endosomal compartment.
研究了脾抗原呈递细胞（APC）和B细胞杂交瘤（LS.102.9）处理和呈递卵清蛋白（OVA）给一组具有不同精细特异性的T-T杂交瘤的能力。脾APC能够处理并将OVA呈递给所有的T-T杂交瘤。B细胞杂交瘤同样能够处理并将OVA呈递给一些T-T杂交瘤，但在刺激其中两个T细胞杂交瘤方面效率很低。亮抑蛋白酶肽可显著增加天然OVA向这两个T-T杂交瘤的呈递。脉冲实验表明，亮抑蛋白酶肽在与主要组织相容性复合体（MHC）分子结合的加工抗原展示于细胞表面之前的步骤作用于APC。亮抑蛋白酶肽对LS.102.9向T-T杂交瘤呈递OVA肽没有影响。亮抑蛋白酶肽抑制LS.102.9在基础条件下产生的OVA表位的生成。我们还研究了其他蛋白酶抑制剂的作用，观察到它们对选定的OVA表位的呈递具有类似的增强和抑制作用。蛋白酶抑制剂对加工的增强表明，在溶酶体/内体区室中，蛋白酶既有生成又有破坏免疫原性肽的能力。我们的数据表明蛋白酶抑制剂可能用作免疫调节剂，并根据溶酶体/内体区室的生理学进行了讨论。
