Faculty of Medicine, Dentistry and Health Sciences Department of Microbiology and Immunology

Doherty Laboratory

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Include: Research Interests | Laboratory Staff | Recent Publications

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Research Interests

Our research examines various aspects of the CD8 T cell response that is generated after virus infection. We currently have four research areas:

  1. The study of factors that influence the quality and quantity of CD8 T cell responses after Influenza A virus infection.
  2. Analysis of the structural features of T cell receptor recognition of viral epitope/MHC complexes.
  3. The comparison and characterisation of influenza A specific CD8 T cell populations and their regulation.
  4. Examination of the quality of cellular immunity generated after the administration of novel vaccine strategies.

Our laboratory uses a combination of cutting edge cellular and molecular immunological techniques to dissect and study virus-specific CD8 T cell responses to both Influenza A virus and HIV virus infection.

This includes techniques such as flow cytometry, cell sorting, influenza A virus reverse genetics, single cell RT-PCR and real time PCR.

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Laboratory Staff

Laureate Professor Peter Doherty
Dr Stephen Turner (Pfizer Fellow, lecturer)
Dr Nicole La Gruta (R.D. Wright Research Fellow)
Dr Katherine Kedzierska (R.D. Wright Research Fellow)
Dr John Stambas (CR Roper Fellow)
Dr Francesca Mercuri (Senior Research Officer (Lab Administrator)
Dr Matthew Olson (Research Officer)

Ms Teresa Rispoli Personal Assistant)

Mr William Rothwell (Fulbright Scholar)

Ms Hayley Croom (Research Assistant)
Ms Natasha Swan (Research Assistant)
Mr Brendan Russ (Research Assistant)

Ms Alice Denton (PhD Student)
Ms E.Bridie Day (PhD Student)
Ms Tania Cukalac (PhD Student)
Ms Lauren Hatton (PhD Student)
Ms Sophie Valkenburg (PhD Students)
Ms Kim Charlton (Honours Student)
Mr Brian Liddicoat (Honours Student)

Sze-Chi (Charlene) Freidanck (Technical Assistant)
Peter Andrew (Technical Assistant)

 
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Recent Publications

List of Publications prior to 2007

  1. Guillonneau C, Mintern J, Hubert F, Hurt A, Besra G, Porcelli S, Barr I, Doherty P, Godfrey D, Turner S. Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity. Proc Nat Acad Sc (USA) 2009; 106: 3330-3335.
  2. Schlub TE, Venturi V, Kedzierska K, Wellard C, Doherty P, Turner S, Ribeiro RM, Hodgkin PD, Davenport MP. Division-linked differentiation can account for CD8(+) T-cell phenotype in vivo. European Journal of Immunology 2009; 39: 67-77.
  3. Sexton A, De Rose R, Reece J, Alcantara S, Loh L, Moffat J, Laurie K, Hurt A, Doherty P, Turner S, Kent S, Stambas J. Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in Macaques. Journal of Virology 2009; 83: 7619.
  4. Kedzierska K, Stambas J, Doherty P. Finding multiple needles in one immune haystack. Nature Methods 2009; 6: 489-490.
  5. Turner S, La Gruta N, Kedzierska K, Thomas PG, Doherty P. Functional implications of T cell receptor diversity. Current Opinion in Immunology 2009; 21: 286-290.
  6. Moffat J, Gebhardt T, Doherty P, Turner S, Mintern J. Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection. European Journal of Immunology 2009; 39: 1203-1210.
  7. Doherty P, Brown L, Kelso A, Thomas PG. Immunity to avian influenza A viruses. OIE Revue Scientifique et Technique 2009; 28: 175-185.
  8. Turner S, Brown L, Doherty P, Kelso A. Q&A: What have we found out about the influenza A (H1N1) 2009 pandemic virus? Journal of Biology 2009; 8: 69-69.4.
  9. Thomas PG, Doherty P. Rules to 'prime' by. Nature Immunology 2009; 10: 14-16.
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  10. Aldridge JR, Moseley CE, Boltz DA, Negovetich NJ, Reynolds C, Franks J, Brown SA, Doherty P, Webster RG, Thomas PG. TNF/iNOS-producing dendric cells are the necessary evil of lethal influenza virus infection. Proc Nat Acad Sc (USA) 2009; 106: 5306-5311.
  11. Thomas PG, Dash P, Aldridge JR, Ellebedy AH, Reynolds C, Funk AJ, Martin WJ, Lamkanfi M, Webby RJ, Boyd KL, Doherty P, Kanneganti T. The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity 2009; 30: 566-75.
  12. Doherty P, Turner S. Thinking about broadly cross-reactive vaccines. Clinical Pharmacology and Therapeutics 2009; 85: 665-668.
  13. Mintern J, Bedoui S, Davey GM, Moffat JM, Doherty P, Turner S. Transience of MHC Class I-restricted antigen presentation after influenza A virus infection. Proc Nat Acad Sc (USA) 2009; 106: 6724-6729.
  14. Jenkins M, La Gruta N, Doherty P, Trapani J, Turner S, Waterhouse N. Visualizing CTL activity for different CD8+ effector T cells supports the idea that lower TCR/epitope avidity may be advantageous for target cell killing. Cell Death & Differentiation 2009; 16: 537-542.
  15. Mintern J, Guillonneau C, Turner S, Doherty P. The immune response to influenza A viruses. In: Influenza Vaccines for the Future, Birkhauser, Basel, 2009:
  16. Doherty P. Burnet, chick embryos, viruses, clones and quantitative biology. Immunology and Cell Biology 2008; 86: 119-123.
  17. Jenkins M, Mintern J, La Gruta N, Kedzierska K, Doherty P, Turner S. Cell cycle-related acquisition of cytotoxic mediators defines the progressive differentiation to effector status for virus-specific CD8+ T cells. Journal of Immunology 2008; 181: 3818-3822.
  18. Kedzierska K, Guillonneau C, Gras S, Hatton L, Webby R, Purcell A, Rossjohn J, Doherty P, Turner S. Complete modification of TCR specificity and repertoire selection does not perturb a CD8+ T cell immunodominance hierarchy. Proc Nat Acad Sc (USA) 2008; 105: 19408-19413.
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  19. Kedzierski L, Curtis JM, Doherty P, Handman E, Kedzierska K. Decreased IL-10 and IL-13 production and increased CD44hi T cell recruitment contribute to Leishmania major immunity induced by non-persistent parasites. European Journal of Immunology 2008; 38: 1-11.
  20. La Gruta N, Thomas P, Webb A, Dunstone M, Cukalac T, Doherty P, PurcellL A, Rossjohn J, Turner S. Epitope-specific TCRβ repertoire diversity imparts no functional advantage on the CD8+ T cell response to cognate viral peptides. Proc Nat Acad Sc (USA) 2008; 105: 2034-2039.
  21. Jenkins M, Trapani J, Doherty P, Turner S. Granzyme K expressing cytotoxic T lymphocytes protects against influenza virus in granzyme AB-/- mice. Viral Immunology 2008; 21: 341-346
  22. Kedzierska K, Venturi V, Valkenburg SA, Davenport M, Turner S, Doherty P. Homogenization of TCR repertoires within secondary CD62Lhigh and CD62Llow virus-specific CD8+ T cell populations. Journal of Immunology 2008; 180: 7938-7947.
  23. Stambas J, Guillonneau C, Kedzierska K, Mintern J, Doherty P, La Gruta N. Killer T cells in influenza. Pharmacology and Therapeutics 2008; 120: 186-196.
  24. Venturi V, Kedzierska K, Tanaka M, Turner S, Doherty P, Davenport M. Method for assessing the similarity between subsets of the T cell receptor repertoire. Journal of Immunological Methods 2008; 329: 67-80.
  25. Rutigliano JA, Doherty P, Franks J, Morris MY, Reynolds C, Thomas PG. Screening monoclonal antibodies for cross-reactivity in the ferret model of influenza infection. Journal of Immunological Methods 2008; 336: 71-77.
  26. Schoenberner A, Center R, Stambas J, Delivannis G, Doherty P, Howard J, Turner S, Purcell D. Sindbis virus vectors elicit hemagglutinin-specific humoral and cellular immune responses and offer a dose-sparing strategy for vaccination. Vaccine 2008; 26: 5641-5648.
  27. Kedzierska K, Thomas P, Venturi V, Davenport M, Doherty P, Turner S, La Gruta N. Terminal deoxynucleotidyltransferase is required for the establishment of private virus-specific CD8+ TCR repertoires and facilitates optimal CTL responses. Journal of Immunology 2008; 181: 2556-2562.
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  28. Doherty P, Kelso A. Toward a broadly protective influenza vaccine. Journal of Clinical Investigation 2008; 118: 3273-3276.
  29. Kedzierska K, La Gruta N, Stambas J, Turner S, Doherty P. Tracking phenotypically and functionally distinct T cell subsets via T cell repertoire diversity. Molecular Microbiology 2008; 45: 607-18.
  30. Day EB, La Gruta N, Doherty P, Turner S. How the structure of viral peptide-MHC complexes influences cytotoxic T cell immunity to viral infections. In: Immunology of Influenza Infection: Approaches for an emerging zoonotic disease. Conference Publication. Research Signpost (Trivandrum), 2008; 33-45.
  31. Ranasinghe C, Turner S, McArthur C, Sutherland D, Kim J, Doherty P, Ramshaw I. Mucosal HIV-1 pox virus prime-boost immunization induces high-avidity CD8+ T cells with regime-dependent cytokine/granzyme B profiles. Journal of Immunology 2007; 178: 2370-2379.
  32. Day EB, Zeng W, Doherty P, Jackson D, Kedzierska K, Turner S. The context of epitope presentation can influence functional quality of recalled influenza A virus-specific memory CD8+ T cells. Journal of Immunology 2007; 179: 2187-2194.
  33. La Gruta N, Kedzierska K, Stambas J, Doherty P. A question of self-preservation: immunopathology in influenza virus infection. Immunology and Cell Biology 2007; 85: 85-92.
  34. Brown SA, Hurwitz JL, Zirkel A, Surman S, Takimoto T, Alymova I, Coleclough C, Portner A, Doherty P, Slobod KS. A recombiant Sendai virus Is controlled by CD4+ effector T cells responding to a secreted Human Immunodeficiency Virus Type 1 envelope glycoprotein. Journal of Virology 2007; 81: 12535-12542.
  35. Stambas J, Doherty P, Turner S. An in vivo cytotoxicity threshold for Influenza A virus-specific effector and memory CD8+ T cells. Journal of Immunology 2007; 178: 1285-1292.
  36. Doherty P. Challenged by complexity: My twentieth century in Immunology. Annual Review of Immunology 2007; 25: 1-19.
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  37. Brent L, Cohen IR, Doherty P, Feldmann M, Matzinger PM, Holgate ST, Lachmann P, Mitchison NA, Nossal G, Rose NR, Zinkernagel R. Crystal-ball gazing - the future of immunological research viewed from the cutting edge. Clinical and Experimental Immunology 2007; 147: 1-10.
  38. Mintern J, Guillonneau C, Carbone F, Doherty P, Turner S. Cutting edge: Tissue-resident memory CTL down-regulate cytolytic molecule expression following virus clearance. Journal of Immunology 2007; 179: 7220-7224.
  39. Turner S, Olivas E, Gutierrez A, Diaz G, Doherty P. Disregulated Influenza A virus-specific CD8+ T cell homeostasis in the absence of IFN-γ signaling. Journal of Immunology 2007; 178: 7616-7622.
  40. Doherty P. Endings and beginnings. Cellular and Molecular Life Sciences 2007; 64: 1-2.
  41. Jenkins M, Kedzierska K, Doherty P, Turner S. Heterogeneity of effector phenotype for acute phase and memory influenza A virus-specific CTL1. Journal of Immunology 2007; 179: 64-70.
  42. Thomas PG, Brown SA, Keating R, Yue W, Morris MY, So J, Webby RJ, Doherty P. Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses. Journal of Immunology 2007; 178: 3091-3098.
  43. Denton AE, Doherty P, Turner S, La Gruta N. IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cells. European Journal of Immunology 2007; 37: 368-375.
  44. Kedzierska K, Stambas J, Jenkins M, Keating R, Turner S, Doherty P. Location rather than CD62L phenothppe is critical in the early establishment of influenza-specific CD8+ T cell memory. Proc Nat Acad Sc (USA) 2007; 104: 9782-9787.
  45. Venturi V, Kedzierska K, Turner S, Doherty P, Davenport M. Methods for comparing the diversity of samples of the T cell receptor repertoire. Journal of Immunological Methods 2007; 321: 182-195.
  46. Doherty P, Turner S. The challenge of viral immunity. Immunity 2007; 27: 363-365.
  47. Keating R, Yue W, Rutigliano JA, So J, Olivas E, Thomas PG, Doherty P. Virus-specific CD8+ T cells in the liver: Armed and ready to kill. Journal of Immunology 2007; 178: 2737-2745.

 

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