Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma

Matthew B. Bloom, Donna Perry-Lalley, Paul F. Robbins, Yong Li, Mona El-Gamil, Steven A. Rosenberg, James C. Yang

Research output: Contribution to journalArticle

Abstract

Recently, major advances have been made in the identification of antigens from human melanoma which are recognized by T cells. In spite of this, little is known about the optimal ways to use these antigens to treat patients with cancer. Progress in this area is likely to require accurate preclinical animal models, but the availability of such models has lagged behind developments in human tumor immunology. Whereas many of the identified human melanoma antigens are normal tissue differentiation proteins, analogous murine tumor antigens have not yet been identified. In this paper we identify a normal tissue differentiation antigen, tyrosinase-related protein 2 (TRP- 2), expressed by the murine B16 melanoma which was found by screening a cDNA library from B16 with tumor-reactive cytotoxic T lymphocytes (CTL). A peptide conforming to the predicted MHC class I H2-Kb binding motif, TRP-2181- 188, was identified as the major reactive epitope within TRP-2 recognized by these anti-B16 CTLs. By site-directed mutagenesis, it was shown that alteration of this epitope eliminated recognition of TRP-2. It was further demonstrated that a CTL line raised from splenocytes by repeated stimulation in vitro with this peptide could recognize B16 tumor and was therapeutic against 3-d-old established pulmonary metastases. The use of TRP-2 in a preclinical model of tumor immunotherapy may be helpful in suggesting optimal vaccination strategies for cancer therapy in patients.

Original languageEnglish (US)
Pages (from-to)453-459
Number of pages7
JournalJournal of Experimental Medicine
Volume185
Issue number3
DOIs
StatePublished - Feb 3 1997
Externally publishedYes

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Experimental Melanomas
Neoplasm Antigens
Melanoma-Specific Antigens
Neoplasms
Cytotoxic T-Lymphocytes
Epitopes
Forensic Anthropology
Peptides
Differentiation Antigens
Human Development
Site-Directed Mutagenesis
Allergy and Immunology
Gene Library
Immunotherapy
dopachrome isomerase
Rejection (Psychology)
Vaccination
Animal Models
Neoplasm Metastasis
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Bloom, M. B., Perry-Lalley, D., Robbins, P. F., Li, Y., El-Gamil, M., Rosenberg, S. A., & Yang, J. C. (1997). Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. Journal of Experimental Medicine, 185(3), 453-459. https://doi.org/10.1084/jem.185.3.453

Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. / Bloom, Matthew B.; Perry-Lalley, Donna; Robbins, Paul F.; Li, Yong; El-Gamil, Mona; Rosenberg, Steven A.; Yang, James C.

In: Journal of Experimental Medicine, Vol. 185, No. 3, 03.02.1997, p. 453-459.

Research output: Contribution to journalArticle

Bloom, MB, Perry-Lalley, D, Robbins, PF, Li, Y, El-Gamil, M, Rosenberg, SA & Yang, JC 1997, 'Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma', Journal of Experimental Medicine, vol. 185, no. 3, pp. 453-459. https://doi.org/10.1084/jem.185.3.453
Bloom, Matthew B. ; Perry-Lalley, Donna ; Robbins, Paul F. ; Li, Yong ; El-Gamil, Mona ; Rosenberg, Steven A. ; Yang, James C. / Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. In: Journal of Experimental Medicine. 1997 ; Vol. 185, No. 3. pp. 453-459.
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