Our Staff

William Kwok

Director of the Tetramer Lab Core at BRI and Member of BRI
Email: 
bkwok@benaroyaresearch.org
Phone: 
206-287-5605

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 principle 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

  1. Chow IT, Kwok WW. Identification of Human Antigen-Specific CD4+ Cells with Peptide-MHC Multimer Technologies. Methods Mol Biol. 2021;2285:153-163. doi: 10.1007/978-1-0716-1311-5_13. PMID: 33928551
  2. DeGottardi Q, Gates T, Yang J, James EA, Malhotra U, Chow I, Simoni Y, Fehlings M, Newell E, DeBerg H, 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
  3. 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). doi: 10.1126/sciimmunol.aax8767. PubMed PMID: 32060144
  4. 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. 2019 Jan;335:68-75. doi: 10.1016/j.cellimm.2018.11.004. Epub 2018 Nov 7. PMID: 30428974
  5. Renand A, Farrington M, Whalen E, Wambre E, Bajzik V, Chinthrajah S, Nadeau KC, Kwok WW. Heterogeneity of Ara h Component-Specific CD4 T Cell Responses in Peanut-Allergic Subjects. Front Immunol. 2018 Jun 25;9:1408. doi: 10.3389/fimmu.2018.01408. eCollection 2018. PMID: 29988522; PMCID: PMC6026622
  6. Wambre E, Bajzik V, DeLong JH, O'Brien K, Nguyen QA, Speake C, Gersuk VH, DeBerg HA, Whalen E, Ni C, Farrington M, Jeong D, Robinson D, Linsley PS, Vickery BP, Kwok WW. A phenotypically and functionally distinct human TH2 cell subpopulation is associated with allergic disorders. Sci Trans Med. 2017;9(401):1-10. doi: 10.1126/scitranslmed.aam9171. PubMed PMID: 28768806
  7. Archila LL, Kwok WW. Tetramer-Guided Epitope Mapping: A Rapid Approach to Identify HLA-Restricted T-Cell Epitopes from Composite Allergens. Methods Mol Biol. 2017;1592:199-209. doi: 10.1007/978-1-4939-6925-8_16. 
  8. Uchtenhagen H, Rims C, Blahnik G, Chow IT, Kwok WW, Buckner JH, James EA. Efficient ex vivo analysis of CD4+ T-cell responses using combinatorial HLA class II tetramer staining. Nat Commun. 2016 Aug 30;7:12614. doi: 10.1038/ncomms12614. PMID: 27571776
  9. James EA, Gates TJ, LaFond RE, Yamamoto S, Ni C, Mai D, Gersuk VH, O'Brien K, Nguyen QA, Zeitner B, Lanteri MC, Norris PJ, Chaussabel D, Malhotra U, Kwok WW. Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome. PLoS Pathog. 2016 Jan 21;12(1):e1005375. doi: 10.1371/journal.ppat.1005375. eCollection 2016
  10. Archila LD, Chow IT, McGinty JW, Renand A, Jeong D, Robinson D, Farrington ML, Kwok WW. Ana o 1 and Ana o 2 cashew allergens share cross-reactive CD4+ T-cell epitopes with other tree nuts. Clin Exp Allergy. Clin Exp Allergy. 2016 Jun;46(6):871-83. doi: 10.1111/cea.12746. PMID: 27129138.
  11. Archila LD, Jeong D, Pascal M, Bartra J, Juan M, Robinson D, Farrington ML, Kwok WW. Jug r 2-reactive CD4+ T cells have a dominant immune role in walnut allergy. J Allergy Clin Immunol. 2015 Oct;136(4):983-92.e7. doi: 10.1016/j.jaci.2015.01.029. Epub 2015 Mar 13. PMC4568181
  12. Chow IT, Yang J, Gates TJ, James EA, Mai DT, Greenbaum C, Kwok WW. Assessment of CD4+ T Cell Responses to Glutamic Acid Decarboxylase 65 Using DQ8 Tetramers Reveals a Pathogenic Role of GAD65 121-140 and GAD65 250-266 in T1D Development. PLoS One. 2014 Nov 18;9 (11):e112882. doi: 10.1371/journal.pone.0112882. eCollection 2014.  PMC4236121
  13. Yang J, Chow IT, Sosinowski T, Torres-Chinn N, Greenbaum CJ, James EA, Kappler JW, Davidson HW, Kwok WW. Autoreactive T cells specific for insulin B:11-23 recognize a low-affinity peptide register in human subjects with autoimmune diabetes. Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):14840-5. doi: 10.1073/pnas.1416864111. Epub 2014 Sep 29. PMC4205657.
  14. Renand A, Newbrough S, Wambre E, DeLong JH, Robinson D, Kwok WW. Arginine kinase Pen m 2 as an important shrimp allergen recognized by TH2 cells. J Allergy Clin Immunol. 2014 Dec;134(6):1456-1459.e7. doi: 10.1016/j.jaci.2014.07.048. Epub 2014 Sep 12. No abstract available. PMC4349443.
  15. McGinty JW, Chow IT, Greenbaum C, Odegard J, Kwok WW, James EA. Recognition of posttranslationally modified GAD65 epitopes in subjects with type 1 diabetes. Diabetes. 2014 Sep;63(9):3033-40. doi: 10.2337/db13-1952. Epub 2014 Apr 4. PMID: 24705406. PMC4392921.
  16. Archila LD, DeLong JH, Wambre E, James EA, Robinson DM, Kwok WW. Grass-specific CD4+ T-cells exhibit varying degrees of cross-reactivity, implications for allergen-specific immunotherapy. Clin Exp Allergy. 2014 Jul;44(7):986-98. doi: 10.1111/cea.12324 PMC4069242.
  17. Chow IT, Yang J, Gates TJ, James EA, Mai DT, Greenbaum C, Kwok WW. Assessment of CD4+ T Cell Responses to Glutamic Acid Decarboxylase 65 Using DQ8 Tetramers Reveals a Pathogenic Role of GAD65 121-140 and GAD65 250-266 in T1D Development. PLoS One. 2014 Nov 18;9 (11):e112882. doi: 10.1371/journal.pone.0112882. eCollection 2014.  PMC4236121.
  18. Wambre E, DeLong JH, James EA, Torres-Chinn N, Pfützner W, Möbs C, Durham SR, Till SJ, Robinson D, Kwok WW. Specific immunotherapy modifies allergen-specific CD4(+) T-cell responses in an epitope-dependent manner. J Allergy Clin Immunol. 2014 Mar;133(3):872-9.e7. doi: 10.1016/j.jaci.2013.10.054. Epub 2013 Dec 25. PMC3961577.
  19. James EA, LaFond RE, Gates TJ, Mai, DT, Malhotra U, Kwok WW. Yellow Fever vaccination elicits broad functional CD4+ T cell responses that recognize structural and non-structural proteins. J Virol. 2013 Dec;87(23):12794-804. doi: 10.1128/JVI.01160-13. PMC3838168.
  20. Yang J, James EA, Sanda S, Greenbaum C, Kwok WW. CD4+ T cells recognize diverse epitopes within GAD65: implications for repertoire development and diabetes monitoring. Immunology 2013 Mar;138(3):269-79. doi: 10.1111/imm.12034. PMC3573280.
  21. Long HM, Chagoury OL, Leese AM, Ryan GB, James E, Morton LT, Abbott RJ, Sabbah S, Kwok WW, Rickinson AB. MHC II tetramers visualize human CD4+ T cell responses to Epstein-Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response. J Exp Med. 2013 May 6;210(5):933-49. doi: 10.1084/jem. PMC3646497
  22. Yang J, James E, Gates TJ, Delong JH, Lafond RE, Malhotra U, Kwok WW. CD4+ T cells recognize unique and conserved 2009 H1N1 influenza hemagglutinin epitopes after natural infection and vaccination. Int Immunol. 2013 Aug;25(8):447-57. doi:10.1093/intimm/dxt005. PMC3720064.
  23. Wambre E, DeLong JH, James EA, LaFond RE, Robinson D, Kwok WW. Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy. J Allergy Clin Immunol. 2012 Feb;129(2):544-51, 551.e1-7. PMC3268867
  24. Bonvalet M, Wambre E, Moussu H, Horiot S, Kwok WW, Louise A, Ebo D, Hoarau C, Van Overtvelt L, Baron-Bodo V, Moingeon P. Comparison between major histocompatibility complex class II tetramer staining and surface expression of activation markers for the detection of allergen-specific CD4⁺ T cells. Clin Exp Allergy. 2011 Jun;41(6):821-9. doi: 10.1111/j.1365-2222.2011.03708.x. Epub 2011 Mar 21. PMID: 21418343.
  25. Bonvalet M, Wambre E, Moussu H, Horiot S, Kwok WW, Louise A, Ebo D, Hoarau C, Van Overtvelt L, Baron-Bodo V, Moingeon P. Comparison between major histocompatibility complex class II tetramer staining and surface expression of activation markers for the detection of allergen-specific CD4⁺ T cells. Clin Exp Allergy. 2011 Jun;41(6):821-9. doi: 10.1111/j.1365-2222.2011.03708.x. Epub 2011 Mar 21. PMID: 21418343.
  26. James EA, Bui J, Berger D, Huston L, Roti M, Kwok WW. Tetramer-guided epitope mapping reveals broad, individualized repertoires of tetanus toxin-specific CD4+ T cells and suggests HLA-based differences in epitope recognition. Int Immunol. 19(11):1291-301, 2007. PMID: 17906339
  27. Bioley G, Jandus C, Tuyaerts S, Rimoldi D, Kwok WW, Speiser DE, Tiercy JM, Thielemans K, Cerottini JC, Romero P. Melan-A/MART-1-specific CD4-T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers. J. Immunol., 177:6769-6779, 2006. PMID: 17082590
  28. 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. 120:21-32, 2006. PMID: 16677863