scholarly journals Identification of Novel Survivin-Derived CTL Epitopes with Different HLA-A-Restriction Profiles

2004 ◽  
Vol 3 (2) ◽  
pp. 173-179 ◽  
Author(s):  
Sine Reker ◽  
Anders Meier ◽  
Lars Holten-Andersen ◽  
Inge Marie Svane ◽  
Jürgen C. Becker ◽  
...  
PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38390 ◽  
Author(s):  
Zhongsheng Guo ◽  
Henghui Zhang ◽  
Huiying Rao ◽  
Dong Jiang ◽  
Xu Cong ◽  
...  

2001 ◽  
Vol 193 (1) ◽  
pp. 73-88 ◽  
Author(s):  
Jan H. Kessler ◽  
Nico J. Beekman ◽  
Sandra A. Bres-Vloemans ◽  
Pauline Verdijk ◽  
Peter A. van Veelen ◽  
...  

We report the efficient identification of four human histocompatibility leukocyte antigen (HLA)-A*0201–presented cytotoxic T lymphocyte (CTL) epitopes in the tumor-associated antigen PRAME using an improved “reverse immunology” strategy. Next to motif-based HLA-A*0201 binding prediction and actual binding and stability assays, analysis of in vitro proteasome-mediated digestions of polypeptides encompassing candidate epitopes was incorporated in the epitope prediction procedure. Proteasome cleavage pattern analysis, in particular determination of correct COOH-terminal cleavage of the putative epitope, allows a far more accurate and selective prediction of CTL epitopes. Only 4 of 19 high affinity HLA-A*0201 binding peptides (21%) were found to be efficiently generated by the proteasome in vitro. This approach avoids laborious CTL response inductions against high affinity binding peptides that are not processed and limits the number of peptides to be assayed for binding. CTL clones induced against the four identified epitopes (VLDGLDVLL, PRA100–108; SLYSFPEPEA, PRA142–151; ALYVDSLFFL, PRA300–309; and SLLQHLIGL, PRA425–433) lysed melanoma, renal cell carcinoma, lung carcinoma, and mammary carcinoma cell lines expressing PRAME and HLA-A*0201. This indicates that these epitopes are expressed on cancer cells of diverse histologic origin, making them attractive targets for immunotherapy of cancer.


2013 ◽  
Vol 31 (3) ◽  
pp. 1051-1058 ◽  
Author(s):  
YU SAWADA ◽  
HIROYUKI KOMORI ◽  
YOSHIYUKI TSUNODA ◽  
MANAMI SHIMOMURA ◽  
MARI TAKAHASHI ◽  
...  

Vaccine ◽  
2005 ◽  
Vol 23 (45) ◽  
pp. 5231-5244 ◽  
Author(s):  
Ningjie Hu ◽  
Celine D'Souza ◽  
Heidi Cheung ◽  
Haili Lang ◽  
Eve Cheuk ◽  
...  

2004 ◽  
Vol 78 (3) ◽  
pp. 1324-1332 ◽  
Author(s):  
Yoshiyuki Yokomaku ◽  
Hideka Miura ◽  
Hiroko Tomiyama ◽  
Ai Kawana-Tachikawa ◽  
Masafumi Takiguchi ◽  
...  

ABSTRACT Investigating escape mechanisms of human immunodeficiency virus type 1 (HIV-1) from cytotoxic T lymphocytes (CTLs) is essential for understanding the pathogenesis of HIV-1 infection and developing effective vaccines. To study the processing and presentation of known CTL epitopes, we prepared Epstein-Barr virus-transformed B cells that endogenously express the gag gene of six field isolates by adopting an env/nef-deletion HIV-1 vector pseudotyped with vesicular stomatitis virus G protein and then tested them for the recognition by Gag epitope-specific CTL lines or clones. We observed that two field variants, SLFNTVAVL and SVYNTVATL, of an A*0201-restricted Gag CTL epitope SLYNTVATL, and three field variants, KYRLKHLVW, QYRLKHIVW, and RYRLKHLVW, of an A24-restricted Gag CTL epitope KYKLKHIVW escaped from being killed by the CTL lines, despite the fact that they were recognized when the synthetic peptides corresponding to these variant sequences were exogenously loaded onto the target cells. Thus, their escape is likely due to the changes that occur during the processing and presentation of epitopes in the infected cells. Mutations responsible for this mode of escape were located within the epitope regions rather than the flanking regions, and such mutations did not influence the virus replication. The results suggest that the impaired antigen processing and presentation often occur in HIV-1 field isolates and thus are one of the major mechanisms that enable HIV-1 to escape from CTL recognition. We emphasize the importance of testing HIV-1 variants in an endogenous expression system.


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