Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes

X. Kang, Yutaka Kawakami, M. El-Gamil, R. Wang, K. Sakaguchi, J. R. Yannelli, E. Appella, S. A. Rosenberg, P. F. Robbins

Research output: Contribution to journalArticle

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Abstract

A number of Ags recognized by class I-restricted, melanoma-specific T cells have recently been identified. In this report we demonstrated that tumor-infiltrating lymphocytes (TIL) from melanoma patient 1413 recognize a tumor Ag, tyrosinase, in the context of HLA-A24. This Ag had previously been shown to be recognized by an HLA-A24-restricted TIL, TIL 888, as well as HLA- A2-restricted, melanoma-specific T cells isolated from two additional patients. The peptide epitope recognized by TIL 1413 was then identified through the use of sequential deletions of the tyrosinase cDNA, as well as through prediction of HLA-A24 binding peptides based on a previously identified motif. Two peptides, a 9-amino acid peptide (AFLPWHRLF) and an overlapping 10-amino acid peptide (AFLPWHRLFL) containing an additional leucine at the carboxyl terminus, were both recognized by TIL 1413. Anti- peptide-specific CTL could be induced by repeated stimulation of peripheral blood lymphocytes from melanoma patient 1413, and this CTL line specifically recognized both HLA-A24+ B cell lines pulsed with the peptide and HLA-A24+ tyrosinase+ melanoma cells. This peptide thus represents a reagent that may be used to generate melanoma-specific T cells for adoptive immunotherapy, as well as in peptide vaccines for HLA-A24+ melanoma patients.

Original languageEnglish
Pages (from-to)1343-1348
Number of pages6
JournalJournal of Immunology
Volume155
Issue number3
Publication statusPublished - 1995
Externally publishedYes

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HLA-A24 Antigen
Tumor-Infiltrating Lymphocytes
Monophenol Monooxygenase
Epitopes
Melanoma
Peptides
T-Lymphocytes
HLA-A2 Antigen
Adoptive Immunotherapy
Amino Acids
Subunit Vaccines
HLA-B Antigens
Leucine
B-Lymphocytes
Complementary DNA
Lymphocytes
Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

Kang, X., Kawakami, Y., El-Gamil, M., Wang, R., Sakaguchi, K., Yannelli, J. R., ... Robbins, P. F. (1995). Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes. Journal of Immunology, 155(3), 1343-1348.

Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes. / Kang, X.; Kawakami, Yutaka; El-Gamil, M.; Wang, R.; Sakaguchi, K.; Yannelli, J. R.; Appella, E.; Rosenberg, S. A.; Robbins, P. F.

In: Journal of Immunology, Vol. 155, No. 3, 1995, p. 1343-1348.

Research output: Contribution to journalArticle

Kang, X, Kawakami, Y, El-Gamil, M, Wang, R, Sakaguchi, K, Yannelli, JR, Appella, E, Rosenberg, SA & Robbins, PF 1995, 'Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes', Journal of Immunology, vol. 155, no. 3, pp. 1343-1348.
Kang X, Kawakami Y, El-Gamil M, Wang R, Sakaguchi K, Yannelli JR et al. Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes. Journal of Immunology. 1995;155(3):1343-1348.
Kang, X. ; Kawakami, Yutaka ; El-Gamil, M. ; Wang, R. ; Sakaguchi, K. ; Yannelli, J. R. ; Appella, E. ; Rosenberg, S. A. ; Robbins, P. F. / Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes. In: Journal of Immunology. 1995 ; Vol. 155, No. 3. pp. 1343-1348.
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AU - Sakaguchi, K.

AU - Yannelli, J. R.

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AB - A number of Ags recognized by class I-restricted, melanoma-specific T cells have recently been identified. In this report we demonstrated that tumor-infiltrating lymphocytes (TIL) from melanoma patient 1413 recognize a tumor Ag, tyrosinase, in the context of HLA-A24. This Ag had previously been shown to be recognized by an HLA-A24-restricted TIL, TIL 888, as well as HLA- A2-restricted, melanoma-specific T cells isolated from two additional patients. The peptide epitope recognized by TIL 1413 was then identified through the use of sequential deletions of the tyrosinase cDNA, as well as through prediction of HLA-A24 binding peptides based on a previously identified motif. Two peptides, a 9-amino acid peptide (AFLPWHRLF) and an overlapping 10-amino acid peptide (AFLPWHRLFL) containing an additional leucine at the carboxyl terminus, were both recognized by TIL 1413. Anti- peptide-specific CTL could be induced by repeated stimulation of peripheral blood lymphocytes from melanoma patient 1413, and this CTL line specifically recognized both HLA-A24+ B cell lines pulsed with the peptide and HLA-A24+ tyrosinase+ melanoma cells. This peptide thus represents a reagent that may be used to generate melanoma-specific T cells for adoptive immunotherapy, as well as in peptide vaccines for HLA-A24+ melanoma patients.

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