Stephen Turner BSc (Hons) PhD
|Academic Degrees||Contact Details|
| 1993: BSc (Hons), Monash University, Clayton, Australia
1997: PhD, Monash University
|Tel: +61 3 8344 8090
Fax: +61 3 8347 1540
Room 3.21A, Department of Microbiology & Immunology
|2007 - present: Pfizer Senior Research Fellow, Department of Microbiology and Immunology, University of Melbourne|
|2011 – present: Professor, Department of Microbiology and Immunology, University of Melbourne|
Professor Stephen Turner
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.
Dr Brendan Russ (Postdoctoral Scientist)
Dr Francesca Mercuri (Influenza Program Project Manager & Laboratory Administrator)
Dr Paul Whitney (NH&MRC CJ Martin Fellow)
Ms Wan-Ting Kan (Laboratory Manager)
Ms Michelle Nguyen (PhD student)
Ms Hayley Croom (PhD Student)
Ms Julia Prier (PhD student)
Ms Sze-Chi Freidanck (Technical Assistant)
NH&MRC Influenza Program Grant “Understanding & Controlling Influenza”
A major collaborative effort is the participation in a National Health & Medical Research Council Program Grant (2010-2014). The Program focuses on two main themes in-order to understand and exploit immune control of influenza virus infection. Theme 1 focuses on understanding the fundamental mechanisms that establish maximum effective cellular immunity, and; Theme 2 focuses on building foundations for the clinical application of strategies to induce cellular immunity to influenza A virus.
There are numerous collaborative projects between the Chief Investigators and Team members within the Department of Microbiology & Immunology at the University of Melbourne (UOM), the WHO Collaborating Centre for Reference and Research on Influenza (WHO), The Ludwig Institute, the School of Population Health UM (SPH) and the CSIRO Australian Animal Health Laboratory (AAHL).
Team Members: Dr Nicole La Gruta, Dr Katherine Kedzierska, Dr Brad Gilbertson, Dr Julie McAuley, Dr Weiguan Zeng, Dr Patrick Reading, Dr Karen Laurie (WHO), Dr Jodie McVernon (SPH), Dr Deb Middleton (AAHL) and Dr Jason Waithman (Ludwig Institute).
- Venturi V, Davenport MP, Swan NG, Doherty PC, Turner SJ, Kedzierska K. Consequences of suboptimal priming are apparent for low avidity T cell responses. Immunol & Cell Biol 2011 (in press).
- Seah, SGK, Sutherland, RM, La Gruta NL, Brown LE, Carrington EM, Belz GT, Brady JL, Turner SJ, Lew AM, Zhan Y. The linear range for detecting antigen-specific T cell frequencies by tetramer staining. Eur J Immunol 2011 (in press).
- Valkenburg, SA, Laurie K, Kels, A, Turner, SJ, Doherty PC, Kedzierska K. T-cell immunity against the A (H1N1)-2009 pandemic virus. Microbiology Australia 2011 (in press)
- Valkenburg SA, Rutigliano JA, Ellebedy AH, Doherty PC, Thomas PG, Kedzierska K. Immunity to seasonal and pandemic influenza A viruses. Microbes Infect 2011 Feb 2. [Epub ahead of print]
- Croom HA, Denton AE, Valkenburg SA, Swan NG, Olso MR, Turner SJ, Doherty PC, Kedzierska K. Memory precursor phenotype of CD8+ T cells reflects early antigenic experience rather than memory numbers in a model of localised acute influenza infection. Eur J Immunol 2011; 41 (3): 682-93.
- Allen S, Turner SJ, Bourges D, Gleeson PA, van Driel, IR. Shaping the T cell repertoire in the periphery. Immunol Cell Biol 2011; 89(1): 60-9.
- Moffat JM, Handel A, Doherty PC, Turner SJ, Thomas PG, La Gruta NL. Influenza epitope-specific CD8+ T cell avidity, but not cytokine polyfunctionality, can be determined by TCRβ clonotype. J Immunol 2010; 185: 6850-6856.
- Turner SJ, Doherty PC, Kelso A. Q&A: H1N1 pandemic flu – What’s new? BMC Biol 2010; 8: 130.
- Valkenburg SA, Gras SG, Guillonneau C, La Gruta NL, Thomas PG, Purcell AW, Rossjohn J, Doherty PC, Turner SJ, Kedzierska K. Protective efficacy of cross-reactive CD8+ T cells recognising mutant viral epitopes depends on peptide-MHC-I structural interactions and avidity. PLoS Pathog 2010; 6: e1001039.
- Valkenburg SA, Day EB, Swan NG, Croom H, Carbone FR, Doherty PC, Turner SJ, Kedzierska K. Consequences of Fixing an Irrelevant TCRα Chain for TCRβ Diversity and Functional Quality of Influenza Virus-Specific CD8+ T Cells. Eur J Immunol 2010; 40: 2470-2481.
- La Gruta NL, Turner SJ. Forewarned is forearmed. Immunity 2010; 33: 5-6.
- Gras S, Kedzierska L, Valkenburg S, Laurie K, Liu YC, Denholm JT, Richards MJ, Rimmelzwaan GF, Kelso A, Doherty PC, Turner SJ, Rossjohn J, Kedzierska K. Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza viruses. Proc Natl Acad Sci USA 2010; 107: 12599-12604.
- Cukalac T, Valkenburg SA, La Gruta NL, Turner SJ, Doherty PC, Kedzierska K. Multiplexed combinatorial tetramer staining in a mouse model of virus infection. J Immunol Methods 2010; 360: 157-161.
- Olson MR, Russ BE, Doherty PC, Turner SJ. The role of epigenetics in the acquisition and maintenance of effector function in virus-specific CD8 T cells. IUBMB Life 2010; 62: 519-526.
- La Gruta NL, Rothwell WT, Cukalac T, Swan NG, Valkenburg SA, Kedzierska K, Thomas PG, Doherty PC, Turner SJ. Primary CTL response magnitude is determined by the extent of naïve T cell recruitment and subsequent clonal expansion. J Clin Invest 2010; 120: 1885-1894.
- Theodossis A, Guillonneau C, Welland A, Ely, LK, Clements CS, Williamson NA, Webb AI, Wilce JA, Mulder RJ, Dunstone MA, Doherty PC, McCluskey J, Purcell AW, Turner SJ*, Rossjohn J*. Constraints within Major-Histocompatibility Complex Class I –restricted peptides: presentation and consequences for T-cell recognition. Proc Natl Acad Sci USA 2010; 107: 5534-5539. *joint senior author
- Olson MR, Russ B, Turner SJ, Stambas J. Influenza A virus-specific CD8+ T cell responses: from induction to function. Future Virol 2010; I5: 175-183.
- Turner SJ, Brown LE, Doherty PC, Kelso A. Q&A: What have we found out about the influenza A (H1N1) 2009 pandemic virus? J Biol 2009; 8: 69.
- Sexton A, De Rose R, Reece JC, Alcantara S, Loh L, Moffat J, Laurie K, Hurt A, Doherty PC, Turner SJ, Kent SJ, Stambas J. Evaluation of recombinant influenza-SIV vaccines in macaques. J Virol 2009; 83: 7619-7628.
- 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.
- Moffat J, 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; 39: 1203-1210.
- 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 2009; 106: 6724-6729.
- La Gruta NL, Kelso A, Brown LE, Chen W, Jackson DC, Turner SJ. The role of CD8+ T cell immunity in influenza disease: potential use in future vaccine development. Expert Rev Resp Med 2009; 3: 523-537.
- Juelich T, Sutcliffe E, Denton A, He Y, Parish C, Turner SJ*, Tremethick D*, Rao S*. Interplay between Chromatin Remodeling and Epigenetic Changes during T cell Lineage-Specific Commitment to Granzyme B Expression. J Immunol 2009; 183: 7063-7072. *authors contributed equally.
- 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.
- 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: 3330-3335.
- Doherty PC, Turner SJ. Thinking about broadly cross-reactive vaccines. Clin Pharmacol Ther 2009; 85: 665-668.
- Doherty PC, Turner SJ. Q&A: What do we know about influenza and what can we do about it? J Biol 2009; 8: 46.
- Cukalac T, Moffat J, Venturi V, Davenport M, Doherty PC, Turner SJ, Stambas J. Narrowed TCR diversity for immunised mice challenged with recombinant influenza A-HIV Env311-320 virus. Vaccine 2009; 27: 6755-6761.
- Turner SJ, La Gruta NL, Kedzierska K, Thomas PG, Doherty PC. Functional implications of T cell receptor diversity. Curr Opin Immunol 2009; 21: 286-290,
- Cheong WS, 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(2): 113-22.