William Kwok , Ph.D.
Affiliate Associate Professor, Immunology

Benaroya Research Institute at Virginia Mason
1201 Ninth Avenue
Seattle, WA 98103
Tel: 206.583-6527
Fax: 206.233-7638
Email: bkwok@benaroyaresearch.org

Dr. K wok received his Ph.D. in Biochemistry from the University of Washington. He joined Benaroya Research Institute in 1986 where now he is a Member. He is the pioneer in development of the HLA class II tetramer technology.

Research Focus

Studies of antigen specific CD4+ T cells have been difficult as these cells are difficult to detect and isolate. The uses of class II tetramers reagents have provided a new approach for studying CD4+ T cells responses. In the past few years, my laboratory has focused on the uses of HLA class II tetramers to probe CD4+ T cells responses in various disease settings in human.

Projects in my laboratory include:
1. Production of class II tetramers. The laboratory is involved in producing more than 25 different HLA class II alleles to study human CD4+ T cell responses under various settings.
2. T cell epitope discovery. A robust approach has been developed in mapping CD4+ T cell epitopes. This approach is used to identify class II restricted T cell epitopes of Categories A, B and C pathogens, tumor antigens and antigens associated with autoimmune diseases in human.
3. Autoimmune disease. Tetramers are used to examine autoreactive CD4+ T cells in diabetes, multiple sclerosis and scleroderma. We also initiate study in using MHC-peptide array chips to examine autoreactive T cells.
4. Examine the molecular mechanism of HLA and autoimmune disease association. HLA that are linked to disease susceptibility or disease protection have been identified. We are interested in the molecular mechanisms that determine the different outcomes.
5. CD8+ suppressors and antigen specific CD4+ Treg. Autoreactive T cells are presence in healthy subjects. Mechanisms must exist that regulate these autoreactive T cells. Our objectives include identifying and characterization of these regulatory T cells.

Recent Publications:

Danke,NA; Kwok, WW. HLA class II-restricted CD4+T cell response directed against influenza viral antigens postinfluenza vaccination. J. Immunol., 171:3163-3169, 2003

Danke, N.A., Koelle, D.M., Yee, C., Beheray, S., and Kwok, W.W. Autoreactive T cells in healthy individuals. J. Immunol., 172:5967-5972, 2004.

Mallone, R., Kochik, S.A. Laughlin, E.M., Gersuk, V.H., Reijonen, H., Kwok, W.W., and Nepom, G.T. Differential recognition and activation thresholds in human autoreactive GAD-specific T-cells. Diabetes, 53:971-977, 2004.

Yang J, Jaramillo A, Shi R, Kwok WW, Mohanakumar T. In vivo biotinylation of the major histocompatibility complex (MHC) class II/peptide complex by coexpression of BirA enzyme for the generation of MHC class II/tetramers. Hum. Immunol., 65:692-9, 2004.

Reijonen H, Mallone R, Heninger AK, Laughlin EM, Kochik SA, Falk B, Kwok WW, Greenbaum C, Nepom GT. GAD65-specific CD4+ T-cells with high antigen avidity are prevalent in peripheral blood of patients with type 1 diabetes. Diabetes, 53:1987-94, 2004.

Yang J, Huston L, Berger D, Danke NA, Liu AW, Disis ML, Kwok WW. Expression of HLA-DP0401 Molecules for Identification of DP0401 Restricted Antigen Specific T Cells. J Clin Immunol. 25(5):428-36, 2005.

Danke NA, Koelle DM, Kwok WW. Persistence of herpes simplex virus type 2 VP16-specific CD4+ T cells. Hum Immunol. 66(7):777-87, 2005.

Danke NA, Yang J, Greenbaum C, and Kwok WW. Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects J. Autoimmun. 25:303-311, 2005.

Oling V, Marttila J, Ilonen J, Kwok WW, Nepom G, Knip M, Simell O, Reijonen H. GAD65- and proinsulin-specific CD4+ T-cells detected by MHC class II tetramers in peripheral blood of type 1 diabetes patients and at-risk subjects. J Autoimmun. 25(3):235-43, 2005.

Yang J, James EA, Huston L, Danke NA, Liu AW, Kwok WW. Multiplex mapping of CD4 T cell epitopes using class II tetramers. Clin Immunol. 120(1):21-32, 2006.

Macaubas C, Wahlstrom J, Galvao da Silva AP, Forsthuber TG, Sonderstrup G, Kwok WW, DeKruyff RH, Umetsu DT. Allergen-specific MHC class II tetramer+ cells are detectable in allergic, but not in nonallergic, individuals. J Immunol. 176(8):5069-77, 2006.

Steere AC, Klitz W, Drouin EE, Falk BA, Kwok WW, Nepom GT, Baxter-Lowe LA. Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide. J Exp Med. 203(4):961-71, 2006.

Yang J, Danke NA, Berger D, Reichstetter S, Reijonen H, Greenbaum C, Pihoker C, James EA, Kwok WW. Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects. J Immunol. 176(5):2781-9, 2006.

Ettinger RA, Papadopoulos GK, Moustakas AK, Nepom GT, Kwok WW. Allelic variation in key peptide-binding pockets discriminates between closely related diabetes-protective and diabetes-susceptible HLA-DQB1*06 alleles. J Immunol. 176(3):1988-98, 2006.

Posted July 2006