Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes

doi:10.1084/jem.180.1.347

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Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes

Y Kawakami, S Eliyahu, K Sakaguchi, PF Robbins, L Rivoltini, JR Yannelli, E Appella and SA Rosenberg
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase- related protein-1 (gp75) were evaluated for recognition by HLA-A2- restricted melanoma-specific cytotoxic T lymphocytes (CTLs) derived from the tumor-infiltrating lymphocytes (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100 (including 3 that also recognized MART-1), but none of the TIL recognized tyrosinase or gp75. Based on the known HLA-A2.1 peptide binding motifs, 23 peptides from MART-1 were synthesized in an attempt to identify the epitopes recognized by TIL. Three peptides were recognized by TIL when pulsed on T2 target cells. One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2-restricted melanoma-specific CTLs. Therefore, this peptide appears to be a very common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be useful for the development of immunotherapeutic strategies.
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McAllister, A., Arbetman, A. E., Mandl, S., Peña-Rossi, C., Andino, R. (2000). Recombinant Yellow Fever Viruses Are Effective Therapeutic Vaccines for Treatment of Murine Experimental Solid Tumors and Pulmonary Metastases. J. Virol. 74: 9197-9205 [Abstract] [Full Text]
Gnjatic, S., Nagata, Y., Jager, E., Stockert, E., Shankara, S., Roberts, B. L., Mazzara, G. P., Lee, S. Y., Dunbar, P. R., Dupont, B., Cerundolo, V., Ritter, G., Chen, Y.-T., Knuth, A., Old, L. J. (2000). Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele. Proc. Natl. Acad. Sci. USA 97: 10917-10922 [Abstract] [Full Text]
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Gomi, S., Nakao, M., Niiya, F., Imamura, Y., Kawano, K., Nishizaka, S., Hayashi, A., Sobao, Y., Oizumi, K., Itoh, K. (1999). A Cyclophilin B Gene Encodes Antigenic Epitopes Recognized by HLA-A24-Restricted and Tumor-Specific CTLs. J. Immunol. 163: 4994-5004 [Abstract] [Full Text]
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Toura, I., Kawano, T., Akutsu, Y., Nakayama, T., Ochiai, T., Taniguchi, M. (1999). Cutting Edge: Inhibition of Experimental Tumor Metastasis by Dendritic Cells Pulsed with {alpha}-Galactosylceramide. J. Immunol. 163: 2387-2391 [Abstract] [Full Text]
Chaux, P., Luiten, R., Demotte, N., Vantomme, V., Stroobant, V., Traversari, C., Russo, V., Schultz, E., Cornelis, G. R., Boon, T., van der Bruggen, P. (1999). Identification of Five MAGE-A1 Epitopes Recognized by Cytolytic T Lymphocytes Obtained by In Vitro Stimulation with Dendritic Cells Transduced with MAGE-A1. J. Immunol. 163: 2928-2936 [Abstract] [Full Text]
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Rosenberg, S. A., Yang, J. C., Schwartzentruber, D. J., Hwu, P., Marincola, F. M., Topalian, S. L., Restifo, N. P., Sznol, M., Schwarz, S. L., Spiess, P. J., Wunderlich, J. R., Seipp, C. A., Einhorn, J. H., Rogers-Freezer, L., White, D. E. (1999). Impact of Cytokine Administration on the Generation of Antitumor Reactivity in Patients with Metastatic Melanoma Receiving a Peptide Vaccine. J. Immunol. 163: 1690-1695 [Abstract] [Full Text]
Rongcun, Y., Salazar-Onfray, F., Charo, J., Malmberg, K.-J., Evrin, K., Maes, H., Kono, K., Hising, C., Petersson, M., Larsson, O., Lan, L., Appella, E., Sette, A., Celis3, E., Kiessling, R. (1999). Identification of New HER2/neu-Derived Peptide Epitopes That Can Elicit Specific CTL Against Autologous and Allogeneic Carcinomas and Melanomas. J. Immunol. 163: 1037-1044 [Abstract] [Full Text]
Butterfield, L. H., Koh, A., Meng, W., Vollmer, C. M., Ribas, A., Dissette, V., Lee, E., Glaspy, J. A., McBride, W. H., Economou, J. S. (1999). Generation of Human T-cell Responses to an HLA-A2.1-restricted Peptide Epitope Derived from {{alpha}}-Fetoprotein. Cancer Res. 59: 3134-3142 [Abstract] [Full Text]
Ronsin, C., Chung-Scott, V., Poullion, I., Aknouche, N., Gaudin, C., Triebel, F. (1999). A Non-AUG-Defined Alternative Open Reading Frame of the Intestinal Carboxyl Esterase mRNA Generates an Epitope Recognized by Renal Cell Carcinoma-Reactive Tumor-Infiltrating Lymphocytes In Situ. J. Immunol. 163: 483-490 [Abstract] [Full Text]
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Prilliman, K. R., Jackson, K. W., Lindsey, M., Wang, J., Crawford, D., Hildebrand, W. H. (1999). HLA-B15 Peptide Ligands Are Preferentially Anchored at Their C Termini. J. Immunol. 162: 7277-7284 [Abstract] [Full Text]
Maitre, N., Brown, J. M., Demcheva, M., Kelley, J. R., Lockett, M. A., Vournakis, J., Cole, D. J. (1999). Primary T-Cell and Activated Macrophage Response Associated with Tumor Protection Using Peptide/Poly-N-Acetyl Glucosamine Vaccination. Clin. Cancer Res. 5: 1173-1182 [Abstract] [Full Text]