Stephen Turner BSc (Hons) PhD

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Include: Bio | Academic degrees | Professional appointments | Research Interests | Recent Publications (2007 — present)

Bio

Academic Degrees:

1993: BSc (Hons), Monash University, Clayton, Australia
1997: PhD, Monash University, Clayton, Australia

Professional Appointments:

2007 — present: Pfizer Senior Research Fellow, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria
2009 — present: Associate Professor, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria

Research Interests

Analysis of factors that determine immunodominance hiearchies

Despite the many potential peptide-MHC combinations that could be recognised by the immune system, T cell responses are generated only to a few of them. Moreover, the size of the T cell response to pathogen derived peptide-MHC complexes falls into a reproducible hierarchy. We utilise a combination of influenza reverse genetics, naïve T cell precursor detection and multi parameter flow cytometry to understand factors that influence the magnitude of T cell responses to acute infection.

Structural determinants of CTL TCR diversity and pMHC recognition

A hallmark of many T cell is the preferred usage of particular T cell receptor combinations. Recent data has suggested a link between TCR diversity and outcome to infection. Given TCR bias is such a characteristic of immunity, we are using a combination of structural biology, retroviral transduction of known influenza-specific TCRs and single cell analysis of TCR repertoire diversity to examine the structural requirements for TCR peptide-MHC recognition, how this influences antigen-specific TCR diversity and how these factors impact the quality of immunity to infection.

Acquisition, epigenetic and transcriptional regulation of CTL gene expression within both effector and memory CTL

Upon activation, naïve T cells undergo a program of proliferation and acquisition of lineage specific functions. Importantly, the factors that regulate acquisition and maintenance of T cell effector function. Furthermore, we are particularly interested in how T cell effector functions acquired during initial activation are maintained into memory. We are using a combination of a single cell RT-PCR technique, identifying novel transcriptional and epigenetic pathways, and over-expression analysis of key regulators to map key events that enable lineage specific T cell function and the establishment of memory. Such analysis will tell us if the molecular mechanisms regulating transcriptional control of T cell effector function are unique and/or shared among key effector genes. This will lead to identification of key immune correlates of protective immunity and will contribute to improvement of immunotherapies for both infectious and autoimmune disease.

Recent Publications (2007 — present)

Original Articles

1. Doherty PC, Turner SJ. Thinking about broadly cross-reactive vaccines. Clin Pharmacol Ther (Accepted 19th March, 2009).
2. Mintern JD, Bedoui S, Davey G, Moffat JM, Doherty PC, Turner SJ. Transience of MHC class I-restricted antigen presentation following influenza A virus infection. Proc Natl Acad Sci USA (Accepted, 4th February, 2009).
3. Moffat, JM, Gebhardt T, Doherty PC, Turner SJ, Mintern, JD. Granzyme A expression reveals distinct cytolytic CTL subsets following Influenza A virus infection. Eur J Immunol 2009 (In press).
4. Guilloneau C, Mintern JD, Hubert F-X, Hurt AC, Besra GS, Barr IG, Doherty PC, Godfrey DI, Turner SJ. α-GalCer administration increases virus-specific T cell memory generation. Proc Natl Acad Sci USA 2009; 106: 3330-3339.
5. Jenkins MR, La Gruta NL, Doherty PC, Trapani JA, Turner SJ, Waterhouse NJ. Visualising CTL activity for different CD8+ effector T cells supports the idea that lower TCR/epitope avidity may be advantageous. Cell, Death Differ 2009; 16: 537-542.
6. Schlub T, Venturi V, Kedzierska K, Wellard C, Doherty PC, Turner SJ, Riberio RM, Hodgkin PD, Davenport MP. Division-linked differentiation can account for CD8+ T cell phenotype in vivo. Eur J Immunol 2009; 39: 67-77.
7. Cheong W-S, Reiseger J, Turner SJ, Boyd R, Netter HJ. Chimeric virus-like particles for the delivery of an inserted conserved influenza A-specific CTL epitope. Antiviral Res 2009; 81: 113-122.
8. Kedzierska K, Guillonneau, Hatton LA, Stockwell D, Gras S, Webby R, Rossjohn J, Purcell AW, Doherty PC, Turner SJ. Complete modification of TCR specificity, repertoire selection and avidity does not alter a CD8+ T cell immunodominance hierarchy. Proc Natl Acad Sci USA 2008; 105: 19408-13.
9. Miller A, Center RJ, Stambas J, Deliyannis G, Doherty PC, Howard JL, Turner SJ, Purcell DF. Sindbis virus vectors elicit hemagglutinin-specific humoral and cellular immune responses and offer a dose-sparing strategy for vaccination. Vaccine 2008; 26: 5641-48.
10. Jenkins MR, Mintern J, La Gruta NL, Kedzierska K, Doherty PC, Turner SJ. Cell-cycle related acquisiton of cytotoxic mediators defines progressive differentiation to effector status for virus-specific CD8+ T cells. J Immunol 2008; 181: 3818-22.
11. Kedzierska K, Thomas PG, Venturi V, Doherty PC, Turner SJ, La Gruta NL. TdT is required for the establishment of private virus-specific CD8+ TCR repertoires and facilitates optimal CTL responses. J Immunol 2008; 181: 2556-62.
12. Gualano RC, Hansen MJ, Vlahos R, Jones JE, Park-Jones RA, Deliyannis G, Turner SJ, Duca KA, Anderson GP. Cigarete smoke worsens lung inflammation and impairs resolution of influenza infection in mice. Resp Res 2008; 9: 53.
13. Rollman E, Turner SJ, Kedzierska K and Kent SJ. Anti-SIV cytolytic molecules in pigtail macaques. AIDS Res Hum Retrov 2008; 4: 1127-31.
14. Jenkins MR, Trapani JA, Doherty PC, Turner SJ. Granzyme K expressing CTL protect against influenza virus in granzyme AB-/- mice. Vir Immunol 2008; 21: 341-46.
15. Kedzierska K, Venturi V, Valkenburg SA, Davenport MP, Turner SJ, Doherty PC. Homogenization of TCR repertoires within Secondary CD62Lhigh and CD62low virus specific CD8+ T cell populations. J Immunol 2008; 180: 7938-47.
16. La Gruta NL, Thomas PG, Webb AI, Dunstone MA, Cukalac T, Doherty PC, Purcell AW, Rossjohn J, Turner SJ. Epitope-specific TCR?repertoire diversity imparts no functional advantage on the CD8+ T cell response to cognate viral peptides. Proc Natl Acad Sci USA 2008; 105: 2034-39.
17. Kedzierska, La Gruta NL, Stambas J, Turner SJ, Doherty PC. Tracking phenotypically and functionally distinct T cell subsets via T cell repertoire diversity. Mol Immunol 2008; 45: 607-61.
18. Halasz P, Holloway G, Turner SJ, Coulson BS. Rotavirus replication in intestinal cells differentially regulates integrin expression by a phosphatidylinositol 3-kinase-dependent pathway resulting in increased cell adhesion and virus yield. J Virol 2008; 82: 148-60.
19. Venturi V, Kedzierska K, Turner SJ, Doherty PC, Davenport M. Method for assessing the similarity between subsets of the T cell receptor repertoire. J Immunol Meth 2008; 329: 67-80.
20. Day EB, La Gruta NL, Doherty PC, Turner SJ. How the structure of viral peptide-MHC complexes influences cytotoxic T cell responses to viral infections. Immunobiology of Influenza infection: Approaches for emerging zoonotic disease. Research Signpost publishers Ltd. Editor: Ralph Tripp, pp33-45, 2008. ISBN 978-81-308-0244-2.
21. Mintern JD, Guillonneau C, Turner SJ, Doherty PC. Influenza Vaccines for the Future. Immunity to Influenza. Birkhauser Publishers Ltd. Editors: Rino Rappuoli & Giuseppe Del Giudice (2007).
22. Mintern JD, Doherty PC, Carbone FR, Turner SJ. Cytolytic granule composition is not maintained by virus-specific memory cytotoxic T lymphocytes. J Immunol 2007; 179: 7220-24.
23. Turner SJ. Fifty years of one powerful idea: 50th Anniversary of Burnet’s clonal selection theory. Australasian Science, 2007.
24. Doherty PC, Turner SJ. The challenges of viral immunity. Immunity 2007; 27: 363-65.
25. Day EB, Kedzierska K, Zheng W, Doherty PC, Jackson DC, Turner SJ. The context of epitope presentation can influence functional quality of recalled Influenza A virus-specific memory CD8+ T cells. J Immunol 2007; 179: 2187-94.
26. Jenkins MR, Kedzierska K, Doherty PC, Turner SJ. Heterogeneity of effector phenotype for acute phase and memory influenza A virus-specific CTL. J Immunol 2007; 179: 64-70.
27. Kedzierska K, Stambas J, Mintern JD, Keating R, Jenkins MR, Turner SJ*, Doherty PC*. Influenza-specific CD8+ T cell memory establishes early in lymph nodes and is not CD62L dependent. Proc Natl Acad Sci USA 2007; 104: 9782-87. [*authors contributed equally]
28. Turner SJ, Olivas E, Gutierrez A, Diaz G, Doherty PC. Disregulated Influenza A virus-specific CD8+ T cell homeostasis in the absence of Interferon-? signalling. J Immunol 2007; 178: 7616-22.
29. Venturi V, Kedzierska K, Turner SJ, Doherty PC, Davenport MP. Methods for comparing the diversity of samples of the T cell receptor repertoire. J Immunol Meth 2007; 321: 182-95.
30. Ranasinghe C, Turner SJ, McArthur C, Sutherland DB, Kim JH, Doherty PC, Ramshaw IA. Mucosal HIV-1 Pox Virus Prime-Boost Immunization Induces High-Avidity CD8+ T Cells with Regime-Dependent Cytokine/Granzyme B Profiles. J Immunol 2007; 178: 2370-79.
31. Stambas J, Doherty PC, Turner SJ. An in vivo cytotoxicity threshold for influenza A virus-specific effector and memory CD8+ T cells. J Immunol 2007; 178: 1285-92.
32. Denton AE, Doherty PC, Turner SJ*, La Gruta NL*. IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cells. Eur J Immunol 2007; 37: 368-75. [*joint senior authorship].