This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhu, B. Articles by Wu, Y. Search for Related Content PubMed PubMed Citation Articles by Zhu, B. Articles by Wu, Y.

Identification of HLA-A*0201-restricted Cytotoxic T Lymphocyte Epitope from TRAG-3 Antigen¹

Cancer Center of People’s Liberation Army, Xinqiao Hospital [B. Z., Z. C., J. G., Z. W., Y. H., D. W.], Institute of Respiratory Diseases, Xinqiao Hospital [X. C.], and Institute of Immunology [B. Z., Z. J., L. Z., Y. W.], Third Military Medical University, Chongqing 400037, and School of Bioengineering, Chongqing Institute of Technology, Chongqing 400050 [Z. L.], China

Purpose: 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.

Experimental Design: 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₍₅₈₆₆₎ (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.

This article has been cited by other articles:

				X.-D. Tang, Y. Wan, L. Chen, T. Chen, S.-T. Yu, Z. Xiong, D.-C. Fang, G.-P. Liang, and S.-M. Yang H-2Kb-Restricted CTL Epitopes from Mouse Heparanase Elicit an Antitumor Immune Response In vivo Cancer Res., March 1, 2008; 68(5): 1529 - 1537. [Abstract] [Full Text] [PDF]

				K. M. Zirlik, D. Zahrieh, D. Neuberg, and J. G. Gribben Cytotoxic T cells generated against heteroclitic peptides kill primary tumor cells independent of the binding affinity of the native tumor antigen peptide Blood, December 1, 2006; 108(12): 3865 - 3870. [Abstract] [Full Text] [PDF]

				B. Janjic, P. Andrade, X.-F. Wang, J. Fourcade, C. Almunia, P. Kudela, A. Brufsky, S. Jacobs, D. Friedland, R. Stoller, et al. Spontaneous CD4+ T Cell Responses against TRAG-3 in Patients with Melanoma and Breast Cancers J. Immunol., August 15, 2006; 177(4): 2717 - 2727. [Abstract] [Full Text] [PDF]

				A. Chen, L. Wang, J. Zhang, L. Zou, Z. Jia, W. Zhou, Y. Wan, and Y. Wu H-2 Kd-Restricted Hepatitis B Virus-Derived Epitope Whose Specific CD8+ T Lymphocytes Can Produce Gamma Interferon without Cytotoxicity J. Virol., May 1, 2005; 79(9): 5568 - 5576. [Abstract] [Full Text] [PDF]