Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma
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...
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The Rockefeller University Press
1997
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196033/ |
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pubmed-21960332008-04-16 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. Article 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, tyrosinaserelated 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. The Rockefeller University Press 1997-02-03 /pmc/articles/PMC2196033/ /pubmed/9053445 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Bloom, Matthew B. Perry-Lalley, Donna Robbins, Paul F. Li, Yong El-Gamil, Mona Rosenberg, Steven A. Yang, James C. |
| spellingShingle |
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 |
| author_facet |
Bloom, Matthew B. Perry-Lalley, Donna Robbins, Paul F. Li, Yong El-Gamil, Mona Rosenberg, Steven A. Yang, James C. |
| author_sort |
Bloom, Matthew B. |
| title |
Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma |
| title_short |
Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma |
| title_full |
Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma |
| title_fullStr |
Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma |
| title_full_unstemmed |
Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma |
| title_sort |
identification of tyrosinase-related protein 2 as a tumor rejection antigen for the b16 melanoma |
| description |
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, tyrosinaserelated 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. |
| publisher |
The Rockefeller University Press |
| publishDate |
1997 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196033/ |
| _version_ |
1611432394323132416 |