Zhang Q J, Chen S S, Saari C A, Massuci M G, Tufaro F, Jefferies W A
Biotechnology Laboratory and Biomedical Research Centre, Medical Genetics and Zoology, University of British Columbia, Vancouver, Canada.
J Immunol. 2000 May 1;164(9):4513-21. doi: 10.4049/jimmunol.164.9.4513.
Recent advances in clarifying the molecular mechanisms involved in Ag processing and presentation have relied heavily on the use of somatic cell mutants deficient in proteasome subunits, TAP transporter, and cell surface expression of MHC class I molecules. Of particular interest currently are those mutants that lack specific protease activity involved in the generation of antigenic peptides. It is theoretically possible that deficiencies of this nature could selectively prevent the cleavage of certain peptide bonds and thus generate only a subset of antigenic peptides. Gro29/Kb cell line is derived from the wild-type murine Ltk- cell line. This cell line is one example of a mutant that lacks specific protease activities. This deficiency manifests itself in an inability to generate a subset of immunodominant peptide epitopes derived from vesicular stomatitis virus and herpes simplex virus. This in turn leads to a general inability to present these viral epitopes to cytotoxic T lymphocytes (CTL). These studies describe a unique Ag processing deficiency and provide new insight into the role of proteasome-independent proteases in MHC class I-restricted peptide generation.
在阐明抗原（Ag）加工与呈递所涉及的分子机制方面，近期的进展在很大程度上依赖于使用蛋白酶体亚基、TAP转运体以及MHC I类分子细胞表面表达缺陷的体细胞突变体。目前特别令人感兴趣的是那些缺乏参与抗原肽生成的特定蛋白酶活性的突变体。从理论上讲，这种性质的缺陷可能会选择性地阻止某些肽键的裂解，从而仅产生一部分抗原肽。Gro29/Kb细胞系源自野生型小鼠Ltk-细胞系。该细胞系是缺乏特定蛋白酶活性的突变体的一个例子。这种缺陷表现为无法产生源自水疱性口炎病毒和单纯疱疹病毒的一部分免疫显性肽表位。这进而导致总体上无法将这些病毒表位呈递给细胞毒性T淋巴细胞（CTL）。这些研究描述了一种独特的抗原加工缺陷，并为非蛋白酶体依赖性蛋白酶在MHC I类限制性肽生成中的作用提供了新的见解。
