Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 21 May 1999:
Vol. 284. no. 5418, pp. 1351 - 1354
DOI: 10.1126/science.284.5418.1351

Reports

Cloning Genes Encoding MHC Class II-Restricted Antigens: Mutated CDC27 as a Tumor Antigen

Rong-Fu Wang, * Xiang Wang, Alicia C. Atwood, Suzanne L. Topalian, Steven A. Rosenberg

In an effort to identify tumor-specific antigens recognized by CD4+ T cells, an approach was developed that allows the screening of an invariant chain-complementary DNA fusion library in a genetically engineered cell line expressing the essential components of the major histocompatibility complex (MHC) class II processing and presentation pathway. This led to the identification of a mutated form of human CDC27, which gave rise to an HLA-DR4-restricted melanoma antigen. A mutated form of triosephosphate isomerase, isolated by a biochemical method, was also identified as an HLA-DR1-restricted antigen. Thus, this approach may be generally applicable to the identification of antigens recognized by CD4+ T cells, which could aid the development of strategies for the treatment of patients with cancer, autoimmune diseases, or infectious diseases.

Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10/2B42, 9000 Rockville Pike, Bethesda, MD 20892, USA.
*   To whom correspondence should be addressed. E-mail: rongfu{at}pop.nci.nih.gov


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cyclin D1-Specific Cytotoxic T Lymphocytes Are Present in the Repertoire of Cancer Patients: Implications for Cancer Immunotherapy.
E. Kondo, B. Maecker, M. R. Weihrauch, C. Wickenhauser, W. Zeng, L. M. Nadler, J. L. Schultze, and M. S. von Bergwelt-Baildon (2008)
Clin. Cancer Res. 14, 6574-6579
   Abstract »    Full Text »    PDF »
Tumor-Associated Galectin-3 Modulates the Function of Tumor-Reactive T Cells.
W. Peng, H. Y. Wang, Y. Miyahara, G. Peng, and R.-F. Wang (2008)
Cancer Res. 68, 7228-7236
   Abstract »    Full Text »    PDF »
Identification of Pro-MMP-7 as a Serum Marker for Renal Cell Carcinoma by Use of Proteomic Analysis.
G. Sarkissian, P. Fergelot, P.-J. Lamy, J.-J. Patard, S. Culine, P. Jouin, N. Rioux-Leclercq, and B. Darbouret (2008)
Clin. Chem. 54, 574-581
   Abstract »    Full Text »    PDF »
EBV Latent Membrane Proteins (LMPs) 1 and 2 as Immunotherapeutic Targets: LMP-Specific CD4+ Cytotoxic T Cell Recognition of EBV-Transformed B Cell Lines.
T. A. Haigh, X. Lin, H. Jia, E. P. Hui, A. T. C. Chan, A. B. Rickinson, and G. S. Taylor (2008)
J. Immunol. 180, 1643-1654
   Abstract »    Full Text »    PDF »
Identification of a Lysosomal Peptide Transport System Induced during Dendritic Cell Development.
O. Demirel, Z. Waibler, U. Kalinke, F. Grunebach, S. Appel, P. Brossart, A. Hasilik, R. Tampe, and R. Abele (2007)
J. Biol. Chem. 282, 37836-37843
   Abstract »    Full Text »    PDF »
Shared MHC Class II-Dependent Melanoma Ribosomal Protein L8 Identified by Phage Display.
R. K. Swoboda, R. Somasundaram, L. Caputo, E. M. Ochoa, P. A. Gimotty, F. M. Marincola, P. Van Belle, S. Barth, D. Elder, D. Guerry, et al. (2007)
Cancer Res. 67, 3555-3559
   Abstract »    Full Text »    PDF »
Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials.
G. Parmiani, A. De Filippo, L. Novellino, and C. Castelli (2007)
J. Immunol. 178, 1975-1979
   Abstract »    Full Text »    PDF »
Potential Side Effects of Dendritic Cells Pulsed with Allogenic Melanoma Cell Lysate in Mice.
S.-Y. Park, W. H. Choi, Y. B. Kim, C. S. Ha, H. Lee, Y.-D. Kwon, O.-M. Choi, Y.-J. Lee, and W. S. Koh (2007)
International Journal of Toxicology 26, 33-40
   Abstract »    Full Text »    PDF »
Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers..
M. Schott (2006)
Endocr. Relat. Cancer 13, 779-795
   Abstract »    Full Text »    PDF »
Unique Tumor Antigens: Evidence for Immune Control of Genome Integrity and Immunogenic Targets for T Cell-Mediated Patient-Specific Immunotherapy.
M. Sensi and A. Anichini (2006)
Clin. Cancer Res. 12, 5023-5032
   Abstract »    Full Text »    PDF »
Spontaneous CD4+ T Cell Responses against TRAG-3 in Patients with Melanoma and Breast Cancers.
B. Janjic, P. Andrade, X.-F. Wang, J. Fourcade, C. Almunia, P. Kudela, A. Brufsky, S. Jacobs, D. Friedland, R. Stoller, et al. (2006)
J. Immunol. 177, 2717-2727
   Abstract »    Full Text »    PDF »
CD4+ T-Cell Response to Mitochondrial Cytochrome b in Human Melanoma.
K. S. Voo, G. Zeng, J.-B. Mu, J. Zhou, X.-Z. Su, and R.-F. Wang (2006)
Cancer Res. 66, 5919-5926
   Abstract »    Full Text »    PDF »
A Novel Strategy for the Discovery of MHC Class II-Restricted Tumor Antigens: Identification of a Melanotransferrin Helper T-Cell Epitope.
T. A. Rohn, A. Reitz, A. Paschen, X. D. Nguyen, D. Schadendorf, A. B. Vogt, and H. Kropshofer (2005)
Cancer Res. 65, 10068-10078
   Abstract »    Full Text »    PDF »
Recognition of a New ARTC1 Peptide Ligand Uniquely Expressed in Tumor Cells by Antigen-Specific CD4+ Regulatory T Cells.
H. Y. Wang, G. Peng, Z. Guo, E. M. Shevach, and R.-F. Wang (2005)
J. Immunol. 174, 2661-2670
   Abstract »    Full Text »    PDF »
A Tumor-Associated Glycoprotein That Blocks MHC Class II-Dependent Antigen Presentation by Dendritic Cells.
R. Gutzmer, W. Li, S. Sutterwala, M. P. Lemos, J. I. Elizalde, S. L. Urtishak, E. M. Behrens, P. M. Rivers, K. Schlienger, T. M. Laufer, et al. (2004)
J. Immunol. 173, 1023-1032
   Abstract »    Full Text »    PDF »
Oct-1 Maintains an Intermediate, Stable State of HLA-DRA Promoter Repression in Rb-defective Cells: AN Oct-1-CONTAINING REPRESSOSOME THAT PREVENTS NF-Y BINDING TO THE HLA-DRA PROMOTER.
A. R. Osborne, H. Zhang, G. Fejer, K. M. Palubin, M. I. Niesen, and G. Blanck (2004)
J. Biol. Chem. 279, 28911-28919
   Abstract »    Full Text »    PDF »
Extensive Replicative Capacity of Human Central Memory T Cells.
M. V. Maus, B. Kovacs, W. W. Kwok, G. T. Nepom, K. Schlienger, J. L. Riley, D. Allman, T. H. Finkel, and C. H. June (2004)
J. Immunol. 172, 6675-6683
   Abstract »    Full Text »    PDF »
Identification of an SSX-2 Epitope Presented by Dendritic Cells to Circulating Autologous CD4+ T Cells.
M. Ayyoub, C. S. Hesdorffer, G. Metthez, S. Stevanovic, G. Ritter, Y.-T. Chen, L. J. Old, D. Speiser, J.-C. Cerottini, and D. Valmori (2004)
J. Immunol. 172, 7206-7211
   Abstract »    Full Text »    PDF »
CD4-Directed Peptide Vaccination Augments an Antitumor Response, but Efficacy Is Limited by the Number of CD8+ T Cell Precursors.
H. L. Hanson, S. S. Kang, L. A. Norian, K. Matsui, L. A. O'Mara, and P. M. Allen (2004)
J. Immunol. 172, 4215-4224
   Abstract »    Full Text »    PDF »
Tolerance and Cancer: Mechanisms of Tumor Evasion and Strategies for Breaking Tolerance.
M. Y. Mapara and M. Sykes (2004)
J. Clin. Oncol. 22, 1136-1151
   Abstract »    Full Text »    PDF »
Evidence for the Presentation of Major Histocompatibility Complex Class I-restricted Epstein-Barr Virus Nuclear Antigen 1 Peptides to CD8+ T Lymphocytes.
K. S. Voo, T. Fu, H. Y. Wang, J. Tellam, H. E. Heslop, M. K. Brenner, C. M. Rooney, and R.-F. Wang (2004)
J. Exp. Med. 199, 459-470
   Abstract »    Full Text »    PDF »
Current Status of Gene Therapy for Lung Cancer and Head and Neck Cancer.
C. Moon, Y. Oh, and J. A. Roth (2003)
Clin. Cancer Res. 9, 5055-5067
   Abstract »    Full Text »    PDF »
Identification of a Colorectal Tumor-Associated Antigen (COA-1) Recognized by CD4+ T Lymphocytes.
C. Maccalli, Y. F. Li, M. El-Gamil, S. A. Rosenberg, and P. F. Robbins (2003)
Cancer Res. 63, 6735-6743
   Abstract »    Full Text »    PDF »
Disease Stage Variation in CD4+ and CD8+ T-Cell Reactivity to the Receptor Tyrosine Kinase EphA2 in Patients with Renal Cell Carcinoma.
T. Tatsumi, C. J. Herrem, W. C. Olson, J. H. Finke, R. M. Bukowski, M. S. Kinch, E. Ranieri, and W. J. Storkus (2003)
Cancer Res. 63, 4481-4489
   Abstract »    Full Text »    PDF »
Histone Deacetylation, But Not Hypermethylation, Modifies Class II Transactivator and MHC Class II Gene Expression in Squamous Cell Carcinomas.
T. Kanaseki, H. Ikeda, Y. Takamura, M. Toyota, Y. Hirohashi, T. Tokino, T. Himi, and N. Sato (2003)
J. Immunol. 170, 4980-4985
   Abstract »    Full Text »    PDF »
Second Class Minors: Molecular Identification of the Autosomal H46 Histocompatibility Locus as a Peptide Presented by Major Histocompatibility Complex Class II Molecules.
H. Sahara and N. Shastri (2003)
J. Exp. Med. 197, 375-385
   Abstract »    Full Text »    PDF »
Rational approaches to human cancer immunotherapy.
I. D. Davis, M. Jefford, P. Parente, and J. Cebon (2003)
J. Leukoc. Biol. 73, 3-29
   Abstract »    Full Text »    PDF »
Identification of HLA-DP3-restricted Peptides from EBNA1 Recognized by CD4+ T Cells.
K. S. Voo, T. Fu, H. E. Heslop, M. K. Brenner, C. M. Rooney, and R.-F. Wang (2002)
Cancer Res. 62, 7195-7199
   Abstract »    Full Text »    PDF »
Multiple HLA Class II-Restricted Melanocyte Differentiation Antigens Are Recognized by Tumor-Infiltrating Lymphocytes from a Patient with Melanoma.
P. F. Robbins, M. El-Gamil, Y. F. Li, G. Zeng, M. Dudley, and S. A. Rosenberg (2002)
J. Immunol. 169, 6036-6047
   Abstract »    Full Text »    PDF »
Revelation of a Cryptic Major Histocompatibility Complex Class II-restricted Tumor Epitope in a Novel RNA-processing Enzyme.
S. L. Topalian, M. I. Gonzales, Y. Ward, X. Wang, and R.-F. Wang (2002)
Cancer Res. 62, 5505-5509
   Abstract »    Full Text »    PDF »
CML28 Is a Broadly Immunogenic Antigen, Which Is Overexpressed in Tumor Cells.
X.-F. Yang, C. J. Wu, L. Chen, E. P. Alyea, C. Canning, P. Kantoff, R. J. Soiffer, G. Dranoff, and J. Ritz (2002)
Cancer Res. 62, 5517-5522
   Abstract »    Full Text »    PDF »
Establishment of 15 Cancer Cell Lines From Patients With Lung Cancer and the Potential Tools for Immunotherapy*.
M. Sugaya, M. Takenoyama, T. Osaki, M. Yasuda, A. Nagashima, K. Sugio, and K. Yasumoto (2002)
Chest 122, 282-288
   Abstract »    Full Text »    PDF »
Identification of a Mutated Fibronectin As a Tumor Antigen Recognized by CD4+T Cells: Its Role in Extracellular Matrix Formation and Tumor Metastasis.
H. Y. Wang, J. Zhou, K. Zhu, A. I. Riker, F. M. Marincola, and R.-F. Wang (2002)
J. Exp. Med. 195, 1397-1406
   Abstract »    Full Text »    PDF »
Adjuvant Immunotherapy of Resected, Intermediate-Thickness, Node-Negative Melanoma With an Allogeneic Tumor Vaccine: Impact of HLA Class I Antigen Expression on Outcome.
J. A. Sosman, J. M. Unger, P.-Y. Liu, L. E. Flaherty, M. S. Park, R. A. Kempf, J. A. Thompson, P. I. Terasaki, and V. K. Sondak (2002)
J. Clin. Oncol. 20, 2067-2075
   Abstract »    Full Text »    PDF »
Autoimmunity to the Mr 32,000 Subunit of Replication Protein A in Breast Cancer.
J. E. Tomkiel, H. Alansari, N. Tang, J. B. Virgin, X. Yang, P. VandeVord, R. L. Karvonen, J. L. Granda, M. J. Kraut, J. F. Ensley, et al. (2002)
Clin. Cancer Res. 8, 752-758
   Abstract »    Full Text »    PDF »
Identification of Cyclin B1 as a Shared Human Epithelial Tumor-Associated Antigen Recognized by T Cells.
H. Kao, J. A. Marto, T. K. Hoffmann, J. Shabanowitz, S. D. Finkelstein, T. L. Whiteside, D. F. Hunt, and O. J. Finn (2001)
J. Exp. Med. 194, 1313-1324
   Abstract »    Full Text »    PDF »
Tumor Antigens Isolated from a Patient with Vitiligo and T-Cell-infiltrated Melanoma.
Y. Kiniwa, T. Fujita, M. Akada, K. Ito, T. Shofuda, Y. Suzuki, A. Yamamoto, T. Saida, and Y. Kawakami (2001)
Cancer Res. 61, 7900-7907
   Abstract »    Full Text »    PDF »
Histone Deacetylase Activity Represses Gamma Interferon-Inducible HLA-DR Gene Expression following the Establishment of a DNase I-Hypersensitive Chromatin Conformation.
A. Osborne, H. Zhang, W.-M. Yang, E. Seto, and G. Blanck (2001)
Mol. Cell. Biol. 21, 6495-6506
   Abstract »    Full Text »    PDF »
Identification and Functional Characterization of Neo-Poly(A) Polymerase, an RNA Processing Enzyme Overexpressed in Human Tumors.
S. L. Topalian, S. Kaneko, M. I. Gonzales, G. L. Bond, Y. Ward, and J. L. Manley (2001)
Mol. Cell. Biol. 21, 5614-5623
   Abstract »    Full Text »    PDF »
Generation of Autologous Tumor-specific T Cell Clones From a Patient With Adenosquamous Carcinoma of the Lung.
T. So, M. Takenoyama, M. Sugaya, M. Yasuda, R. Eifuku, T. Yoshimatsu, T. Hanagiri, T. Oyama, M. Kodate, T. Osaki, et al. (2001)
Jpn. J. Clin. Oncol. 31, 311-317
   Abstract »    Full Text »    PDF »
Combinatorial Peptide Libraries as an Alternative Approach to the Identification of Ligands for Tumor-reactive Cytolytic T Lymphocytes.
C. Pinilla, V. Rubio-Godoy, V. Dutoit, P. Guillaume, R. Simon, Y. Zhao, R. A. Houghten, J.-C. Cerottini, P. Romero, and D. Valmori (2001)
Cancer Res. 61, 5153-5160
   Abstract »    Full Text »    PDF »
The immunoprotective MHC II epitope of a chemically induced tumor harbors a unique mutation in a ribosomal protein.
T. Matsutake and P. K. Srivastava (2001)
PNAS 98, 3992-3997
   Abstract »    Full Text »    PDF »
CD4+ T cell recognition of MHC class II-restricted epitopes from NY-ESO-1 presented by a prevalent HLA DP4 allele: Association with NY-ESO-1 antibody production.
G. Zeng, X. Wang, P. F. Robbins, S. A. Rosenberg, and R.-F. Wang (2001)
PNAS
   Abstract »    Full Text »
Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen.
T. Ono, T. Kurashige, N. Harada, Y. Noguchi, T. Saika, N. Niikawa, M. Aoe, S. Nakamura, T. Higashi, A. Hiraki, et al. (2001)
PNAS 98, 3282-3287
   Abstract »    Full Text »    PDF »
Invariant chains with the class II binding site replaced by a sequence from influenza virus matrix protein constrain low-affinity sequences to MHC II presentation.
C. Carstens, D. K. Newman, H. Bohlen, A. Konig, and N. Koch (2000)
Int. Immunol. 12, 1561-1568
   Abstract »    Full Text »    PDF »
The Serpin Secreted by Brugia malayi Microfilariae, Bm-SPN-2, Elicits Strong, but Short-Lived, Immune Responses in Mice and Humans.
X. Zang, A. K. Atmadja, P. Gray, J. E. Allen, C. A. Gray, R. A. Lawrence, M. Yazdanbakhsh, and R. M. Maizels (2000)
J. Immunol. 165, 5161-5169
   Abstract »    Full Text »    PDF »
Identification of a Tumor-specific Shared Antigen Derived From an Eph Receptor and Presented to CD4 T Cells on HLA Class II Molecules.
R. Chiari, G. Hames, V. Stroobant, C. Texier, B. Maillère, T. Boon, and P. G. Coulie (2000)
Cancer Res. 60, 4855-4863
   Abstract »    Full Text »
NY-ESO-1 Encodes DRB1*0401-restricted Epitopes Recognized by Melanoma-reactive CD4+ T Cells.
H. M. Zarour, W. J. Storkus, V. Brusic, E. Williams, and J. M. Kirkwood (2000)
Cancer Res. 60, 4946-4952
   Abstract »    Full Text »
Identification of T Cell Ligands in a Library of Peptides Covalently Attached to HLA-DR4.
E. Boen, A. R. Crownover, M. McIlhaney, A. J. Korman, and J. Bill (2000)
J. Immunol. 165, 2040-2047
   Abstract »    Full Text »    PDF »
Identification of CD4+ T Cell Epitopes from NY-ESO-1 Presented by HLA-DR Molecules.
G. Zeng, C. E. Touloukian, X. Wang, N. P. Restifo, S. A. Rosenberg, and R.-F. Wang (2000)
J. Immunol. 165, 1153-1159
   Abstract »    Full Text »    PDF »
T Cell Adoptive Immunotherapy of Newly Diagnosed Gliomas.
G. E. Plautz, D. W. Miller, G. H. Barnett, G. H. J. Stevens, S. Maffett, J. Kim, P. A. Cohen, and S. Shu (2000)
Clin. Cancer Res. 6, 2209-2218
   Abstract »    Full Text »
Identification of a MHC Class II-Restricted Human gp100 Epitope Using DR4-IE Transgenic Mice.
C. E. Touloukian, W. W. Leitner, S. L. Topalian, Y. F. Li, P. F. Robbins, S. A. Rosenberg, and N. P. Restifo (2000)
J. Immunol. 164, 3535-3542
   Abstract »    Full Text »    PDF »
Melan-A/MART-151-73 represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4+ T cells.
H. M. Zarour, J. M. Kirkwood, L. S. Kierstead, W. Herr, V. Brusic, C. L. Slingluff Jr., J. Sidney, A. Sette, and W. J. Storkus (2000)
PNAS 97, 400-405
   Abstract »    Full Text »    PDF »
A Novel Putative Low-Affinity Insulin-like Growth Factor-binding Protein, LIBC (Lost in Inflammatory Breast Cancer), and RhoC GTPase Correlate with the Inflammatory Breast Cancer Phenotype.
K. L. van Golen, S. Davies, Z. Fen Wu, Y. Wang, C. D. Bucana, H. Root, S. Chandrasekharappa, M. Strawderman, S. P. Ethier, and S. D. Merajver (1999)
Clin. Cancer Res. 5, 2511-2519
   Abstract »    Full Text »    PDF »
CD4+ T cell recognition of MHC class II-restricted epitopes from NY-ESO-1 presented by a prevalent HLA DP4 allele: Association with NY-ESO-1 antibody production.
G. Zeng, X. Wang, P. F. Robbins, S. A. Rosenberg, and R.-F. Wang (2001)
PNAS 98, 3964-3969
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)