Rodriguez G M, Diment S
Michael Heidelberger Division of Immunology, Department of Pathology, New York University Medical Center, New York 10016, USA.
Eur J Immunol. 1995 Jul;25(7):1823-7. doi: 10.1002/eji.1830250705.
Most native antigens require digestion by acidic proteases in order to be recognized in the context of major histocompatibility complex class II by T helper cells (Th). We have studied the roles of three different acidic proteases, cathepsin D, cathepsin B and cathepsin L, in the processing of ovalbumin (OVA) for presentation in the context of I-Ad. We report that digestion of OVA in vitro with the aspartyl protease cathepsin D generates the epitope OVA322-336, which is recognized by I-Ad-restricted OVA-specific Th in the presence of paraformaldehyde-fixed antigen-presenting cells (APC). In contrast, digestion of OVA with the cysteine proteases cathepsin B and L not only failed to generate an epitope, but also destroyed OVA322-336. In the presence of fixed APC expressing I-Ad. OVA322-336 was protected from destructive proteolysis by cathepsin L. These results illustrate the dependence of epitope selection on the intracellular proteolytic environment in APC, and suggest that mechanisms must exist for protection of epitopes from destructive proteolysis in the processing compartments.
大多数天然抗原需要被酸性蛋白酶消化，才能在主要组织相容性复合体II类分子的背景下被辅助性T细胞（Th）识别。我们研究了三种不同的酸性蛋白酶，组织蛋白酶D、组织蛋白酶B和组织蛋白酶L，在卵清蛋白（OVA）加工过程中以I-Ad为背景进行呈递的作用。我们报告称，用天冬氨酸蛋白酶组织蛋白酶D在体外消化OVA可产生表位OVA322-336，在存在多聚甲醛固定的抗原呈递细胞（APC）的情况下，该表位可被I-Ad限制的OVA特异性Th识别。相比之下，用半胱氨酸蛋白酶组织蛋白酶B和L消化OVA不仅未能产生表位，还破坏了OVA322-336。在表达I-Ad的固定APC存在的情况下，OVA322-336受到组织蛋白酶L的保护而不被破坏性蛋白水解。这些结果说明了表位选择对APC内细胞内蛋白水解环境的依赖性，并表明在加工区室中必须存在保护表位免受破坏性蛋白水解的机制。
