López D, Del Val M
Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Madrid, Spain.
J Immunol. 1997 Dec 15;159(12):5769-72.
CTL recognize peptides derived from protein Ags bound to MHC-class I molecules. Proteasomes probably participate in the generation of these peptide epitopes. We investigated the role of proteasomes in the presentation of endogenously synthesized short viral proteins. To this end, we employed proteasome and cysteine protease inhibitors and two closely related recombinant vaccinia viruses that code for 17- and 19-amino acid-long products encompassing murine CMV 9pp89 epitope. Presentation of both minigene products required processing to shorter peptides and was independent of ubiquitination. Proteasomes were necessary for processing the 17-mer product, and cysteine proteases were not required. In contrast, the 19-mer product could be processed in parallel either by proteasomes or by cysteine proteases independently. These results highlight the diversity of alternative processing pathways even for short peptidic Ags, provide evidence for the involvement of cysteine proteases in MHC class I presentation, and show that cleavage by cysteine proteases is governed by sequences flanking the epitope.
细胞毒性T淋巴细胞（CTL）识别与MHC-I类分子结合的蛋白质抗原衍生的肽段。蛋白酶体可能参与这些肽表位的产生。我们研究了蛋白酶体在呈现内源性合成的短病毒蛋白中的作用。为此，我们使用了蛋白酶体和半胱氨酸蛋白酶抑制剂以及两种密切相关的重组痘苗病毒，它们编码包含鼠巨细胞病毒9pp89表位的17和19个氨基酸长的产物。两种小基因产物的呈递都需要加工成更短的肽段，并且与泛素化无关。蛋白酶体对于加工17聚体产物是必需的，而不需要半胱氨酸蛋白酶。相反，19聚体产物可以由蛋白酶体或半胱氨酸蛋白酶独立地并行加工。这些结果突出了即使对于短肽抗原而言替代加工途径的多样性，为半胱氨酸蛋白酶参与MHC-I类呈递提供了证据，并表明半胱氨酸蛋白酶的切割受表位侧翼序列的支配。
