表位
CTL公司*
成纤维细胞
细胞毒性T细胞
分子生物学
抗原
蛋白酵素
肽
体外
蛋白酶
寡肽
酶
生物化学
生物
化学
免疫学
作者
Federica Albo,Antonella Cavazza,Bruno Giardina,Mario Marini,L.Giorgio Roda,Reto Schumacher,Giulio C. Spagnoli
标识
DOI:10.1016/j.bbagen.2004.01.006
摘要
Degradation of the tumor antigen epitope gp100(280-288) (YLEPGPVTA) was investigated in the presence of cultured human fibroblasts, and acellular supernatants obtained from these cells; the possible effect of substrate degradation on in vitro immunorecognition was also addressed. In the presence of fibroblasts, gp100(280-288) was degraded to free amino acids with a half-life of less than 4 min; hydrolysis data support the hypothesis that substrate degradation was mainly caused by the activity of cell-expressed amino- and carboxypeptidases. Gp100(280-288) was also degraded in the presence of acellular supernatants: under these conditions, the hydrolysis pattern was similar to that observed in the presence of whole cells, but degradation kinetics was slower. As a result of these phenomena, immunorecognition of gp100(280-288)-specific cytotoxic T lymphocyte (CTL) clones was severely hampered, and was totally suppressed after 90 min. In conclusion, the high activity of fibroblast-expressed proteases, and the presence of wide-scope soluble enzymes, may explain, at least in part, the low activity of peptide-based antineoplastic vaccines, as well as the transient effectiveness of subcutaneously administered peptides in general.
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