1. Class I-restricted antigen processing and presentation
2. Mechanism of determinant selection and immunodominance hierarchy
3. T cell memory development and maintenance
4. Human tumour immune response and cancer vaccine
5. Regulatory T cells

• Joe Wei - Ph.D. Student

Our lab is interested in cellular immunology. More specifically, the mechanisms governing T cell determinant selection, the factors set immunodominance hierarchy-a phenomenon that the immune system often focuses on very limited T cell determinants from complex antigen or pathogen, and the contribution of the immunoproteasome to immunodominance and thymic selection. We use various approaches and animal models (transgenic and knockout mice) to address the related issues. We routinely analyse CD8+ T cell responses ex vivo using tetramer and intracellular cytokine staining methods. We also establish T cell lines to assess antigen processing and presentation properties of various antigen presenting cells in the presence or absence of various inhibitors.

Part of the reason for studying immunodominance hierarchy and determinant selection is to use the acquired knowledge to lead better vaccine design for infectious diseases and tumours. Naturally, a better vaccine design involves the following two important aspects: one is to maximally stimulate the immune system and the other is to maximally maintain the stimulated response as a recallable memory pool. So, we are also exploring ways that enhance CD8+ T cell priming and subsequent memory formation. In the human anti-tumour setting, we focus on determinant discovery and tumour infiltrating regulatory T cells.

1. Chen, W, Luis C. Antón, Jack R. Bennink, Jonathan W. Yewdell. (2000) Dissecting the Multi-Factorial Causes of Immunodominance in Class I Restricted T Cell Responses to Viruses. Immunity. 12:83-93.

2. Weisan Chen, Christopher C. Norbury, Yunjung Cho, Jonathan W. Yewdell, and Jack R. Bennink. (2001) Immunoproteasomes Shape Immunodominance Hierarchies of Antiviral CD8+ T Cells at the Levels of T Cell Repertoire and Presentation of Viral Antigens. J. Exp. Med. 193: 1319-1326.

3. Weisan Chen, Paul A. Calvo, Daniela Malide, James Gibbs, Ulrich Schubert, Igor Bacik, Sameh Basta, Robert O'neill, Jeanne Schickli, Peter Palese, Peter Henklein, Jack R. Bennink & Jonathan W. Yewdell. (2001) A Novel Influenza A Virus Mitochondrial Protein That Induces Cell Death. Nature Medicine 7:1306-1312.

4. Weisan Chen, Kelly-Anne Masterman, Sameh Basta, Nektaria Dimopoulos, Barbara Knowles, Jack R. Bennink, and Jonathan W. Yewdell. (2004) Cross-Priming of CD8 + T Cells by Viral and Tumor Antigens is a Robust Phenomenon. European J Immunology. 34:194-199.

5. Qiyuan Chen, Heather Jackson, Philip Parente, Tina Luke, Mark Rizkalla, Tsin Yee Tai, He-Cheng Zhu, Nicole Mifsud, Nektaria Dimopoulos, Kelly-Ann Masterman, Wendie Hopkins, Heather Goldie, Eugene Maraskovsky, Simon Green, Lena Miloradovic, James McCluskey, Lloyd Old, Ian Davis, Jonathan Cebon, Weisan Chen. (2004) Immunodominant CD4+ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant. PNAS 101:9363~9368.

6. Ian D. Davis, Weisan Chen, Heather Jackson, Phillip Parente, Mark Shackleton, Wendie Hopkins, Qiyuan Chen, Roger Murphy, Andrew Scott, Eugene Maraskovsky, Grant McArthur, Duncan MacGregor, Simon Green, Andrew Cuthbertson, Darryl Maher4, Lena Miloradovic, Sue Mitchell, Gerd Ritter, Elisabeth Stockert, Eric W. Hoffman, Lloyd J. Old, Jonathan S. Cebon. (2004) Vaccination with recombinant NY-ESO-1 protein formulated in ISCOM® induces a broad integrated CD4+ and CD8+ T cell and humoral immune response in cancer patients with minimal residual disease. PNAS 101:10607~10702.

7. Weisan Chen, Ken Pang, Kelly-Anne Masterman, Gina Kennedy, Sameh Basta, Nektaria Dimopoulos, Felicita Hornung, Mark Smyth, Jack R. Bennink, and Jonathan W. Yewdell. (2004) Reversal in the Immunodominance Hierarchy in Secondary CD8+ T Cell Responses to Influenza A Virus: Roles for Cross-Presentation and Lysis-Independent Immunodomination J. Immunol 173:5021-5027

8. Heather Jackson, Nektaria Dimopoulos, Tsin Yee Tai, Qiyuan Chen, Nicole A Mifsud, Suzanne Svobodova, Judy Browning, Immanuel Luescher, Lloyd J. Old, Ian D Davis, Jonathan Cebon, Weisan Chen (2006). Striking immunodominance hierarchy of naturally-occurring CD8+ and CD4+ T cell responses to NY-ESO-1. J. Immunol. 176:5908-5917

9. Ken C. Pang, Megan T. Sanders, John J. Monaco, Peter C. Doherty, Stephen J. Turner, Weisan Chen. (2006) Immunoproteasome subunit deficiencies impact differentially upon two immunodominant influenza virus specific CD8+ T cell responses Journal of Immunology 177: 7680-7688

10. Weisan Chen and James McCluskey. Immunodominance and immunodomination: (2006) Critical Factors in Developing Effective CD8+ T Cell Based-Cancer Vaccines. Invited review article for Advances in Cancer Research. 95:203-247