DOI: 10.1084/jem.185.3.453. Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma

Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma

10.1084/jem.185.3.453

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

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, 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.

Bibliography

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. The Journal of Experimental Medicine, 185(3), 453â460.

Authors 7

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

References 24 Referenced 333

10.1093/jnci/86.15.1159 / J Natl Cancer Inst / Treatment of patients with metastatic melanoma with autologous tumorinfiltrating lymphocytes and interleukin 2 by Rosenberg (1994)
10.1084/jem.178.2.489 / J Exp Med / The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas by Brichard (1993)
{'key': '2023072507134765800_B3', 'first-page': '3124', 'article-title': 'Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy (erratum published 54:3952)', 'volume': '54', 'author': 'Robbins', 'year': '1994', 'journal-title': 'Cancer Res'} / Cancer Res / Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy (erratum published 54:3952) by Robbins (1994)
10.1084/jem.181.2.799 / J Exp Med / Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31-restricted tumor-infiltrating lymphocytes (erratum published 181:1261) by Wang (1995)
10.1073/pnas.91.9.3515 / Proc Natl Acad Sci USA / Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor by Kawakami (1994)
10.1073/pnas.91.14.6458 / Proc Natl Acad Sci USA / Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection by Kawakami (1994)
10.1016/S0022-2836(05)80360-2 / J Mol Biol / Basic local alignment search tool by Altschul (1990)
10.1002/j.1460-2075.1992.tb05083.x / EMBO (Eur Mol Biol Organ) J / A second tyrosinase-related protein, TRP-2, maps to and is mutated at the mouse slaty locus by Jackson (1992)
10.1007/BF00172063 / Immunogenetics / MHC ligands and peptide motifs: first listing by Rammensee (1995)
{'key': '2023072507134765800_B10', 'first-page': '7', 'article-title': 'Identification of T cell epitopes using allele-specific ligand motifs', 'volume': '95', 'author': 'Stevanovic', 'year': '1994', 'journal-title': 'Behring Inst Mitt'} / Behring Inst Mitt / Identification of T cell epitopes using allele-specific ligand motifs by Stevanovic (1994)
10.1084/jem.183.3.1185 / J Exp Med / A mutated betacatenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes by Robbins (1996)
10.1002/ijc.2910500220 / Int J Cancer / Precursor frequency analysis of human cytolytic T lymphocytes directed against autologous melanoma cells by Coulie (1992)
10.1126/science.1840703 / Science (Wash DC) / A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma by van der Bruggen (1991)
10.1084/jem.179.3.921 / J Exp Med / Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes by Gaugler (1994)
10.1016/S1074-7613(95)80053-0 / Immunity / BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes by Boel (1995)
10.1084/jem.182.3.689 / J Exp Med / A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma by Van den Eynde (1995)
10.1126/science.7652577 / Science (Wash DC) / A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma by Wolfel (1995)
10.1016/0248-4900(94)90001-9 / Biol Cell / Identification and characterization of the tumor-specific P1A gene product by Amar-Costesec (1994)
10.1084/jem.173.6.1373 / J Exp Med / The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice by Van den Eynde (1991)
10.1002/eji.1830220916 / Eur J Immunol / Mouse tumor rejection antigens P815A and P815B: two epitopes carried by a single peptide by Lethe (1992)
10.1002/eji.1830241125 / Eur J Immunol / Localization of two cytotoxic T lymphocyte epitopes and three anchoring residues on a single nonameric peptide that binds to H-2Ld and is recognized by cytotoxic T lymphocytes against mouse tumor P815 by Van den Eynde (1994)
10.1038/369067a0 / Nature (Lond) / CTL induction by a tumour-associated antigen octapeptide derived from a murine lung carcinoma by Mandelboim (1994)
10.1084/jem.184.2.647 / J Exp Med / Identification of epitope mimics recognized by CTL reactive to the melanoma/melanocyte-derived peptide MART1(27–35) by Loftus (1996)
10.1084/jem.184.6.2207 / J Exp Med / Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes by Wang (1996)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:49 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 3:49 a.m.)
Indexed	1 week, 2 days ago (Aug. 27, 2025, 11:49 a.m.)
Issued	28 years, 7 months ago (Feb. 3, 1997)
Published	28 years, 7 months ago (Feb. 3, 1997)
Published Online	28 years, 7 months ago (Feb. 3, 1997)
Published Print	28 years, 7 months ago (Feb. 3, 1997)

Funders 0

None

BibTeX

@article{Bloom_1997, title={Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma}, volume={185}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.185.3.453}, DOI={10.1084/jem.185.3.453}, number={3}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Bloom, Matthew B. and Perry-Lalley, Donna and Robbins, Paul F. and Li, Yong and El-Gamil, Mona and Rosenberg, Steven A. and Yang, James C.}, year={1997}, month=feb, pages={453–460} }

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