Identification and modification of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from Ran antigen |
| |
Authors: | Fan Li Di Yang Yiqin Wang Baohua Liu Yijing Deng Li Wang Xiaoyun Shang Weidong Tong Bing Ni Yuzhang Wu |
| |
Institution: | (1) Department of Immunology, Institute of Immunology, Third Military Medical University, 400038 Chongqing, China;(2) Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 400042 Chongqing, China;(3) Department of Nephrology, Xinqiao Hospital, Third Military Medical University, 400037 Chongqing, China;(4) Department of Geriatric Gastroenterology, Chinese PLA General Hospital, 28 FuXing Street, 100853 Beijing, China |
| |
Abstract: | Ran is considered to be a promising target for tumor-specific immunotherapy because its protein is exclusively expressed in
tumor tissues, though its mRNA can be expressed in most normal tissues. In our study, we obtained four candidate wild-type
epitopes designated Ran1, Ran2, Ran3, and Ran4, derived from the Ran antigen with the highest predicted affinity with MHC-I,
indicated by affinity prediction plots and molecular dynamics simulation. However, in vitro affinity assays of these epitopes
showed only a moderate affinity with MHC-I. Thus, we designed altered peptide ligands (APLs) derived from Ran wild-type epitopes
with preferred primary and auxiliary HLA-A*0201 molecule anchor residue replacement. Of the eight tested peptides, the 1Y
analog had the strongest binding-affinity and lowest-dissociation rate to HLA-A*0201. Additionally, we investigated the CTLs
activities induced by Ran wild-type peptides and the APLs in human PBMCs and in HLA-A*0201/Kb transgenic mice. Ran1 1Y was superior to other APLs and wild-type peptides in eliciting epitope-specific CTL immune responses
both in vitro and in vivo. In summary, a wild-type epitope of the tumor-specific antigen Ran, expressed broadly in many tumors,
was identified and designated Ran1. An APL of Ran1, Ran1 1Y, was further designed and verified in vitro and in vivo and found
to elicit a stronger Ran-specific CTL response, indicating a potential anti-tumor application in the future. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|