William Kwok, PhD
Background Information
Dr. Kwok received his bachelor’s degree in Biochemistry from the University of Wisconsin. After completing his PhD in Biochemistry at the University of Washington in 1983, he remained in Seattle completing post-doctoral research work at the Fred Hutchinson Cancer Research Center before moving to the Virginia Mason Research Center (later renamed the Benaroya Research Institute at Virginia Mason). Since 1988, he has been a principal investigator at the Benaroya Research Institute.
Area of Research
Dr. Kwok's research projects are focused on understanding the behavior of human “helper” T cells. These cells are difficult to detect and isolate using traditional methods, but can be studied effectively using tetramers: synthetic protein conjugates that can be used to directly label T cells. These novel tetramer reagents provide a new approach for studying healthy immune responses directed against viruses and other pathogens and harmful immune responses that are the underlying cause of autoimmune diseases and allergy. Detailed studies using tetramers have increased our understanding of the biochemical patterns that activate the immune system. Knowledge of this kind will be critical for developing improved vaccines and targeted therapies to combat infectious diseases, allergy and autoimmunity.
Featured Publications
Chow IT, Kwok WW. Identification of Human Antigen-Specific CD4+ Cells with Peptide-MHC Multimer Technologies. Methods Mol Biol. 2021;2285:153-163. 2021 Apr 30. doi: 10.1007/978-1-0716-1311-5_13. PMID: 33928551
Boddul SV, Sharma RK, Dubnovitsky A, Raposo B, Gerstner C, Shen Y, Iyer VS, Kasza Z, Kwok WW, Winkler AR, Klareskog L, Malmström V, Bettini M, Wermeling F. In vitro and ex vitro functional characterization of human HLA-DRB1∗04 restricted T cell receptors. J Transl Autoimmun. 2021 Mar 3;4:100087. doi: 10.1016/j.jtauto.2021.100087. PMID: 33768201 | PMC7980064
Cook L, Rees WD, Wong MQ, Kwok WW, Levings MK, Steiner TS. Recurrent Clostridioides difficile infection is associated with impaired Th17 immunity to TcdB. Gastroenterology. 2020 Nov 27;S0016-5085(20)35510-4. doi: 10.1053/j.gastro.2020.11.043. PMID: 33253683
Leonard MM, Silvester JA, Leffler D, Fasano A, Kelly CP, Lewis SK, Goldsmith JD, Greenblatt E, Kwok WW, McAuliffe WJ, Galinsky K, Siegelman J, Chow IT, Wagner JA, Sapone A, Smithson G. Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial. Gastroenterology. 2020 Oct 29:S0016-5085(20)35330-0. doi: 10.1053/j.gastro.2020.10.040. PMID: 33130104
Wang J, Jelcic I, Mühlenbruch L, Haunerdinger V, Toussaint NC, Zhao Y, Cruciani C, Faigle W, Naghavian R, Foege M, Binder TMC, Eiermann T, Opitz L, Fuentes-Font L, Reynolds R, Kwok WW, Nguyen JT, Lee JH, Lutterotti A, Münz C, Rammensee HG, Hauri-Hohl M, Sospedra M, Stevanovic S, Martin R. HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis. Cell. 2020 Oct 14:S0092-8674(20)31251-4. doi: 10.1016/j.cell.2020.09.054. PMID: 33091337 | PMC7707104
DeGottardi Q, Gates TJ, Yang J, James EA, Malhotra U, Chow IT, Simoni Y, Fehlings M, Newell EW, DeBerg HA, Kwok WW. Ontogeny of different subsets of yellow fever virus-specific circulatory CXCR5+ CD4+ T cells after yellow fever vaccination. Sci Rep. 2020 Sep 24;10(1):15686. doi: 10.1038/s41598-020-72610-6. PMID: 32973217 | PMC7519049
Muehling LM, Heymann PW, Wright PW, Eccles JD, Agrawal R, Carper HT, Murphy DD, Workman LJ, Word CR, Ratcliffe SJ, Capaldo BJ, Platts-Mills TAE, Turner RB, Kwok WW, Woodfolk JA. Human Th1 and Th2 Cells Targeting Rhinovirus and Allergen Coordinately Promote Allergic Asthma. J Allergy Clin Immunol. 2020 Apr 19. pii: S0091-6749(20)30494-2. doi: 10.1016/j.jaci.2020.03.037. PMID: 32320734 | PMC7483727
Zhao LP, Papadopoulos GK, Kwok WW, Moustakas AK, Bondinas GP, Carlsson A, Elding Larsson H, Ludvigsson J, Marcus C, Samuelsson U, Wang R, Pyo CW, Nelson WC, Geraghty DE, Lernmark Å. Next-Generation HLA Sequence Analysis Uncovers Seven HLA-DQ Amino Acid Residues and Six Motifs Resistant to Childhood Type 1 Diabetes. Diabetes. 2020 Nov;69(11):2523-2535. doi: 10.2337/db20-0374. Epub 2020 Aug 31. PMID: 32868339 | PMC7576571
Barone SM, Paul AGA, Muehling LM, Lannigan JA, Kwok WW, Turner RB, Woodfolk JA, Irish JM. Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection, and cancer therapy. bioRxiv. 2020 Aug 1:2020.07.31.190454. doi: 10.1101/2020.07.31.190454. PMID: 32766581 | PMC7402038
Larson D, Patel P, Salapatek AM, Couroux P, Whitehouse D, Pina A, Johnson JL, Sever ML, Sanda S, Poyser J, Allio T, Scadding GW, Qin T, Shamji MH, Kwok WW, James EA, French D, Lelic A, Larché M, Altman MC, Togias A, Durham SR. Nasal Allergen Challenge and Environmental Exposure Chamber Challenge: A Randomized Trial Comparing Clinical and Biological Responses to Cat Allergen. J Allergy Clin Immunol. 2020 Jun;145(6):1585-1597. doi: 10.1016/j.jaci.2020.02.024. Epub 2020 Mar 10. PMID: 32169380
Gerstner C, Turcinov S, Hensvold AH, Chemin K, Uchtenhagen H, Ramwadhdoebe TH, Dubnovitsky A, Kozhukh G, Rönnblom L, Kwok WW, Achour A, Catrina AI, van Baarsen LGM, Malmström V. Multi-HLA class II tetramer analyses of citrulline-reactive T cells and early treatment response in rheumatoid arthritis. BMC Immunol. 2020 May 18;21(1):27. doi: 10.1186/s12865-020-00357-w. PMID: 32423478 | PMC7236297
Arribas-Layton D, Guyer P, Delong T, Dang M, Chow IT, Speake C, Greenbaum CJ, Kwok WW, Baker RL, Haskins K, James EA. Hybrid Insulin Peptides are Recognized by Human T Cells in the Context of DRB1*04:01. Diabetes. 2020 Apr 14. pii: db190620. doi: 10.2337/db19-0620. PMID: 32291282 | PMC7306133
Zhao LP, Papadopoulos GK, Kwok WW, Moustakas AK, Bondinas GP, Larsson HE, Ludvigsson J, Marcus C, Samuelsson U, Wang R, Pyo CW, Nelson WC, Geraghty DE, Lernmark Å. Motifs of Three HLA-DQ Amino Acid Residues (α44, β57, β135) Capture Full Association with the Risk of Type 1 Diabetes in DQ2 and DQ8 Children. Diabetes. 2020 Apr 3. pii: db200075. doi: 10.2337/db20-0075. PMID: 32245799 | PMC7306123
Wen X, Yang J, James E, Chow IT, Reijonen H, Kwok WW. Increased islet antigen-specific regulatory and effector CD4+ T cells in healthy individuals with the type 1 diabetes-protective haplotype. Sci Immunol. 2020 Feb 14;5(44). pii: eaax8767. doi: 10.1126/sciimmunol.aax8767. PMID: 32060144 | PMC7566980
Chow IT, Gates TJ, Papadopoulos GK, Moustakas AK, Kolawole EM, Notturno RJ, McGinty JW, Torres-Chinn N, James EA, Greenbaum C, Nepom GT, Evavold BD, Kwok WW. Discriminative T cell recognition of cross-reactive islet-antigens is associated with HLA-DQ8 transdimer-mediated autoimmune diabetes. Sci Adv. 2019 Aug 21;5(8):eaaw9336. doi: 10.1126/sciadv.aaw9336. eCollection 2019 Aug. PMID: 31457096 | PMC6703875
Free ME, Stember KG, Hess JJ, McInnis EA, Lardinois O, Hogan SL, Hu Y, Mendoza C, Le AK, Guseman AJ, Pilkinton MA, Bortone DS, Cowens K, Sidney J, Karosiene E, Peters B, James E, Kwok WW, Vincent BG, Mallal SA, Jennette JC, Ciavatta DJ, Falk RJ. Restricted myeloperoxidase epitopes drive the adaptive immune response in MPO-ANCA vasculitis. J Autoimmun. 2019 Aug 2:102306. doi: 10.1016/j.jaut.2019.102306. PMID: 31383567 | PMC6650447
Speake C, Bahnson HT, Wesley JD, Perdue N, Friedrich D, Pham MN, Lanxon-Cookson E, Kwok WW, Sehested Hansen B, von Herrath M, Greenbaum CJ. Systematic Assessment of Immune Marker Variation in Type 1 Diabetes: A Prospective Longitudinal Study. Front Immunol. 2019 Sep 13;10:2023. doi: 10.3389/fimmu.2019.02023. eCollection 2019. PMID: 31572352 | PMC6753618
Rudulier CD, Tonti E, James E, Kwok WW, Larché M. Modulation of CRTh2 expression on allergen-specific T cells following peptide immunotherapy. Allergy. 2019 May 11. doi: 10.1111/all.13867. PMID: 31077596 | PMC6817377
Longino NV, Yang J, Iyer JG, Ibrani D, Chow IT, Laing KJ, Campbell VL, Paulson KG, Kulikauskas RM, Church CD, James EA, Nghiem P, Kwok WW, Koelle DM. Human CD4+ T cells specific for Merkel cell polyomavirus localize to Merkel cell carcinomas and target a required oncogenic domain. Cancer Immunol Res. 2019 Aug 12. pii: canimm.0103.2019. doi: 10.1158/2326-6066.CIR-19-0103. PMID: 31405946 | PMC6438725
Zhao LP, Papadopoulos GK, Kwok WW, Xu B, Kong M, Moustakas AK, Bondinas GP, Carlsson A, Elding-Larsson H, Ludvigsson J, Marcus C, Persson M, Samuelsson U, Wang R, Pyo CW, Nelson WC, Geraghty DE, Lernmark Å. Eleven Amino Acids of HLA-DRB1 and Fifteen Amino Acids of HLA-DRB3, 4 and 5 Include Potentially "Causal Residues" Responsible for the Risk of Childhood Type 1 Diabetes. Diabetes. 2019 May 24. pii: db190273. doi: 10.2337/db19-0273. PMID: 31127057 | PMC6692811
Chow IT, Gates TJ, Papadopoulos GK, Moustakas AK, Kolawole EM, Notturno RJ, McGinty JW, Torres-Chinn N, James EA, Greenbaum C, Nepom GT, Evavold BD, Kwok WW. Discriminative T cell recognition of cross-reactive islet-antigens is associated with HLA-DQ8 transdimer-mediated autoimmune diabetes. Sci Adv. 2019 Aug 21;5(8):eaaw9336. doi: 10.1126/sciadv.aaw9336. eCollection 2019 Aug. PMID: 31457096 | PMC6703875
Ackermann C, Smits M, Woost R, Eberhard JM, Peine S, Kummer S, Marget M, Kuntzen T, Kwok WW, Lohse AW, Jacobs T, Boettler T, Schulze Zur Wiesch J. HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules. Sci Rep. 2019 Jul 23;9(1):10624. doi: 10.1038/s41598-019-47024-8. PMID: 31337800 | PMC6650447
Ruff WE, Dehner C, Kim WJ, Pagovich O, Aguiar CL, Yu AT, Roth AS, Vieira SM, Kriegel C, Adeniyi O, Mulla MJ, Abrahams VM, Kwok WW, Nussinov R, Erkan D, Goodman AL, Kriegel MA. Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity. Cell Host Microbe. 2019 Jun 17. pii: S1931-3128(19)30248-3. doi: 10.1016/j.chom.2019.05.003. PMID: 31227334 | PMC8194364
Boonpiyathad T, Sokolowska M, Morita H, Rückert B, Kast JI, Wawrzyniak M, Sangasapaviliya A, Pradubpongsa P, Fuengthong R, Thantiworasit P, Sirivichayakul S, Kwok WW, Ruxrungtham K, Akdis M, Akdis CA. Der p 1-specific regulatory T cell response during house dust mite allergen immunotherapy. Allergy. 2018 Nov 28. doi: 10.1111/all.13684. PMID: 30485456
Wang Y, Sosinowski T, Novikov A, Crawford F, White J, Jin N, Liu Z, Zou J, Neau D, Davidson HW, Nakayama M, Kwok WW, Gapin L, Marrack P, Kappler JW, Dai S. How C-terminal additions to insulin B-chain fragments create superagonists for T cells in mouse and human type 1 diabetes. Sci Immunol. 2019 Apr 5;4(34). pii: eaav7517. doi: 10.1126/sciimmunol.aav7517. PMID: 30952805 | PMC6929690
Hung SC, Hou T, Jiang W, Wang N, Qiao SW, Chow IT, Liu X, van der Burg SH, Koelle DM, Kwok WW, Sollid LM, Mellins ED. Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense. J Immunol. 2019 Mar 29. pii: ji1801454. doi: 10.4049/jimmunol.1801454. PMID: 30926644 | PMC6494460
Blahnik G, Uchtenhagen H, Chow IT, Speake C, Greenbaum C, Kwok WW, James EA. Analysis of pancreatic beta cell specific CD4+ T cells reveals a predominance of proinsulin specific cells. Cell Immunol. 2018 Nov 7. pii: S0008-8749(18)30273-9. doi: 10.1016/j.cellimm.2018.11.004. PMID: 30428974
James EA, Gillette L, Durinovic-Bello I, Speake C, Bondinas GP, Moustakas AK, Greenbaum CJ, Papadopoulos GK, Kwok WW. DRB4*01:01 Has a Distinct Motif and Presents a Proinsulin Epitope That Is Recognized in Subjects with Type 1 Diabetes. J Immunol. 2018 Nov 19. pii: ji1800723. doi: 10.4049/jimmunol.1800723. PMID: 30455401 | PMC6426329