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

Brooks Laboratory

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Include: Research Interests | Major Research Projects | Laboratory Staff | Recent Publications

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Dr. Andrew Brooks' Home Page

Research Interests

Our research is largely centred on immune responses to viral infection in both humans and animal models of disease. The immune response to pathogens is remarkably diverse often consisting of responses by cells of the innate immune system such as NK cells, dendritic cells and neutrophils, together with populations of antigen-specific T and B cells. Our laboratory is interested in how responses from these diverse arms of the immune system are integrated to provide effective anti-viral immunity.

We have made use of a number of models of herpes simplex virus type 1 (HSV-1) and influenza virus infection to assess the role of innate cells such as NK cells and neutrophils in the early inflammatory response to viral infection. This work has largely compared the cell types recruited to diverse sites of infection in these models of infection and assessed their ability to control viral replication in distinct anatomical sites.

We are also assessing the role of virus-specific CD8 T cells in transplantation. Cytomegalovirus (CMV), a member of the herpes family of viruses is a major cause of morbidity following transplantation. It has been hypothesized that in addition to playing a role in limiting viral replication, CMV-specific T cells may also induce graft rejection via recognition of allogeneic MHC. We have established systems to monitor CMV-specific CD8 T cell responses in lung transplant recipients and are currently assessing their capacity to recognise both virus-infected cells and the allogeneic lung transplant. In this context we have recently demonstrated that the non-classical class I molecule HLA-E, which is thought to primarily act as a ligand for natural killer cell receptors can also be recognised by CMV-specific CD8 T cells. These HLA-E restricted CMV-specific T cells have been shown to directly recognise a large number of allogeneic target cells. Consequently we are trying to understand the contribution of these cells in the context of transplantation where they may both assist in controlling the spread of CMV but may also directly recognise allogeneic grafts leading to rejection.

Major Research Projects

  1. The role of NK cells in the immune response to herpes simplex virus
  2. Identification and characterisation of HSV-1 specific CD4 T cells.
  3. The role of neutrophils in respiratory infections
  4. The function of non classical MHC class I molecules
  5. The role of cytomegalovirus-specific T cells in transplantation
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Laboratory Staff

Research Staff

Dr Patrick Reading (R.D Wright Fellow)
Dr Lucy Sullivan (Doherty Fellow)
Dr Jie Lin (Research Officer)
Mr Darryl Johnson (Research Assistant)
Ms Danielle Pickett (Research Assistant)

Post graduate students

Ms Michelle Tate (PhD Student)
Mr Paul Whitney (PhD Student)
Ms Emma Job (Honours Student)
Ms Aislin Meehan (Honours Student)

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Recent Publications

List of Publications prior to 2007

  1. Bedoui S, Whitney P, Waithman J, Eidsmo L, Wakim L, Caminschi I, Allan R, Wojtasiak M, Shortman K, Carbone F, Brooks A, Heath W. Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nature Immunology 2009; 10: 488-495.
  2. Pellicci D, Patel O, Kjer-Nielsen L, Pang SS, Sullivan L, Kyparissoudis K, Brooks A, Reid HH, Gras S, Lucet IS, Koh R, Smyth MJ, Mallevaey T, Matsuda JL, Gapin L, McCluskey J, Godfrey D, Rossjohn J. Differential recognition of CD1d-α-galactosyl ceramide by the Vβ8.2 Vβ7 semi-invariant NKT T cell receptors. Immunity 2009; 31: 47-59.
  3. Gras S, Burrows SR, Kjer-Nielsen L, Clements CS, Liu YC, Bell MJ, Brooks A, Purcell A, McCluskey J, Sullivan L, Rossjohn J. The shaping of T cell receptor recognition by self-tolerance. Immunity 2009; 30: 193-203.
  4. Tran PD, Christiansen D, Winterhalter A, Brooks A, Gorrell M, Lilienfeld BG, Seeback JD, Sandrin M, Sharland A. Porcine cells express more than one functional ligand for the human lymphocyte activating receptor NKG2D. Xenotransplantation 2008; 15: 321-332.
  5. Reading P, Bozza S, Gilbertson B, Tate M, Moretti S, Job E, Crouch E, Brooks A, Brown L, Romani L, Bottazzi B, Mantovani A. Antiviral activity of the long chain pentraxin PTX3 against influenza viruses. Journal of Immunology 2008; 180: 3391-3398.
  6. Silva A, Andrews D, Brooks A, Smyth M, Hayakawa Y. Application of CD27 as a marker for distinguishing human NK cell subsets. International Immunology 2008; 20: 625-630.
  7. Petrie E, Clements C, Lin J, Sullivan L, Johnson D, Huyton T, Heroux A, Hoare H, Beddoe T, Rossjohn J, Brooks A, Wilce M, Reid H. CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence. Journal of Experimental Medicine 2008; 205: 725-35.
  8. Rollman E, Mason RD, Lin J, Brooks A, Kent S. Protection afforded by live attenuated SIV is associated with rapid killing kinetics of CTLs. Journal of Medical Primatology 2008; 37 Supp 2: 24-32.
  9. Hoare H, Sullivan L, Clements C, Ely L, Beddoe T, Henderson K, Lin J, Reid H, Brooks A, Rossjohn J. Subtle changes in peptide conformation profoundly affect recognition of the non-classical MHC class I molecule HLA-E by the CD94-NKG2 natural killer cell receptors. Journal of Molecular Biology 2008; 377: 1297-1303.
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  10. Sullivan L, Clements C, Rossjohn J, Brooks A. The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity. Tissue Antigens 2008; 72: 415-424.
  11. Tate MD, Brooks A, Reading P. The role of neutrophils in the the upper and lower respiratory tract during influenza virus infection of mice Respiratory Research 2008; 9: 57-69.
  12. Reading P, Job E, Tate M, Brooks A, Bottazzi B, Mantovani A. Inhibition of Influenza Viruses By Proteins of the Innate Immune System. In: Options for the Control of Influenza VI. International Medical Press(London). 2008; 489-491.
  13. Barr DP, Belz G, Reading P, Wojtasiak M, Whitney PG, Heath W, Carbone F, Brooks A. A role for plasmacytoid dendritic cells in the rapid IL-18-dependent activation of NK cells following HSV-1 infection. European Journal of Immunology 2007; 37: 1334-42.
  14. Westall G, Brooks A, Kotsimbas T. CD8+ T-cell maturation following lung transplantation: The differential impact of CMV and acute rejection. Transplant Immunology 2007; 18: 186-192.
  15. Reading P, Tate MD, Pickett DL, Brooks A. Glycosylation as a target for recognition of influenza viruses by the innate immune system. Advances in Experimental Medicine and Biology 2007; 598: 279-292.
  16. Reading P, Whitney PG, Barr DP, Wojtasiak M, Mintern J, Waithman JC, Brooks A. IL-18, but not IL-12, regulates NK cell activity following intranasal Herpes Simplex Virus Type 1 infection. Journal of Immunology 2007; 179: 3214-3221.
  17. Rollman E, Smith MZD, Brooks A, Purcell D, Zuber B, Ramshaw I, Kent S. Killing kinetics of Simian immunodeficiency virus-specific CD8+ T cells: Implications for HIV vaccine strategies. Journal of Immunology 2007; 179: 4571-4579.
  18. Sullivan L, Clements C, Beddoe T, Johnson D, Hoare H, Lin J, Huyton T, Hopkins E, Reid H, Wilce M, Kabat J, Borrego F, Coligan J, Rossjohn J, Brooks A. The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition. Immunity 2007; 27: 900-911.

 

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