Identification of HLA-A*0201-restricted cytotoxic T lymphocyte epitope from TRAG-3 antigen.
OBJECTIVE
Identification of tumor antigen and subsequent identification of T-cell epitope from these antigens make specific immunotherapy for malignant tumor applicable. Because TRAG-3 antigen is expressed in most melanomas and 54% of non-small cell lung carcinomas and HLA-A2.1-expressing individuals cover >50% in the population of China, we aim at identifying TRAG-3-encoded peptide presented by HLA-A2.1.


METHODS
In our study, a HLA-A2.1-restricted CTL epitope was identified by using the following four-step procedure: (a) computer-based epitope prediction from the amino acid sequence of TRAG-3 antigen; (b) peptide-binding assay to determine the affinity of the predicted peptide with HLA-A2.1 molecule; (c) stimulation of primary T-cell response against the predicted peptides in vitro; and (d) testing of the induced CTLs toward LB373-MEL cells expressing TRAG-3 antigen and HLA-A2.1.


RESULTS
Of the four tested peptides, effectors induced by a peptide of TRAG-3 at residue position 58-66 lysed LB373-MEL cells expressing both TRAG-3 and HLA-A2.1. Our results indicate that peptide TRAG-3(58 approximately 66) (ILLRDAGLV) is a new HLA-A2.1-restricted CTL epitope capable of inducing TRAG-3 specific CTLs in vitro.


CONCLUSIONS
Because TRAG-3 is a cancer/testis antigen expressed in most melanomas and half of non-small cell lung carcinomas, identification of the TRAG-3/HLA-A2.1 peptide ILLRDAGLV may facilitate peptide-based specific immunotherapy for various histological tumors.
Zhu
Bo
B
Cancer Center of People's Liberation Army, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Chen
Zhengtang
Z
Cheng
Xiaoming
X
Lin
Zhihua
Z
Guo
Jianxiu
J
Jia
Zhengcai
Z
Zou
Liyun
L
Wang
Zhixin
Z
Hu
Yide
Y
Wang
Dongling
D
Wu
Yuzhang
Y
D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D007111:Immunity, Cellular; D008175:Lung Neoplasms; D008545:Melanoma / Q000276:immunology; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; C118809:CSAG2 protein, human; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D009363:Neoplasm Proteins; D010446:Peptide Fragments