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.
- The role of NK cells in the immune response to herpes simplex virus
- Identification and characterisation of HSV-1 specific CD4 T cells.
- The role of neutrophils in respiratory infections
- The function of non classical MHC class I molecules
- The role of cytomegalovirus-specific T cells in transplantation
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)
- Andrews DM, Sullivan LC, Baschuk N, Chan CJ, Berry R, Cotterell CL, Lin J, Halse H, Watt SV,
Poursine-Laurent J, Wang CR, Scalzo AA, Yokoyama WM, Rossjohn J, Brooks AG*, Smyth MJ*.
Recognition of the nonclassical MHC class I molecule H2-M3 by the receptor Ly49A regulates the
licensing and activation of NK cells.
Nature Immunol 2012; doi:10.1038/ni.2468.
* Joint Senior and Corresponding Author
- Zeng L, Sullivan LC, Vivian JP, Walpole NG, Harpur CM, Rossjohn J, Clements CS, Brooks AG. A structural basis for antigen presentation by the MHC class Ib molecule, Qa-1b. Journal of Immunology 2012; 188: 302-310.
- Tate MD, Brooks AG, Reading PC, Mintern JD.
Neutrophils sustain effective CD8(+) T-cell responses in the respiratory tract following influenza infection.
Immunology and Cell Biology 2012; 90: 197-205.
[C1] Impact factor 3.741 Citations 1 [R: 5, P:50, W:30]
- Jegaskanda S, Reece JC, De Rose R, Stambas J, Sullivan L, Brooks AG, Kent SJ, Sexton A. Comparison of Influenza and SIV Specific CD8 T Cell Responses in Macaques. PLoS One 2012; 7: e32431.
- Hofstetter AR, Ford ML, Sullivan LC, Wilson JJ, Hadley A, Brooks AG, Lukacher AE. MHC Class Ib-Restricted CD8 T Cells Differ in Dependence on CD4 T Cell Help and CD28 Costimulation over the Course of Mouse Polyomavirus Infection. Journal of Immunology 2012; 88: 3071-3079.
- Tate MD, Brooks AG, Reading PC, Mintern JD. Neutrophils sustain effective CD8(+) T-cell responses in the respiratory tract following influenza infection. Immunol Cell Biol 2012; 90(2): 197-205.
- Wun KS, Cameron G, Patel O, Pang SS, Pellicci DG, Sullivan LC, Keshipeddy S, Young MH, Uldrich AP, Thakur MS, Richardson SK, Howell AR, Illarionov PA, Brooks AG, Besra GS, McCluskey J, Gapin L, Porcelli SA, Godfrey DI, Rossjohn J. A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells. Immunity 2011; 34: 327-339.
- Vivian JP, Duncan RC, Berry R, O'Connor GM, Reid HH, Beddoe T, Gras S, Saunders PM,
Olshina MA, Widjaja JM, Harpur CM, Lin J, Maloveste SM, Price DA, Lafont BA, McVicar DW,
Clements CS, Brooks* AG, Rossjohn* J.
Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B.
Nature 2011; 479: 401-405.
* Joint Senior and Corresponding Author
- Uldrich AP, Patel O, Cameron G, Pellicci DG, Day EB, Sullivan LC, Kyparissoudis K, Kjer-Nielsen L, Vivian JP, Cao B, A. Brooks AG, Williams SJ, Illarionov P, Besra GS, Turner SJ, Porcelli SA, McCluskey J, Smyth MJ, Rossjohn J, Godfrey DI. A semi-invariant Valpha10+ T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties. Nature Immunology 2011; 12: 616-623.
- Tate, M. D., H. C. Schilter HC, A. G. Brooks AG, and P. C. Reading PC. Responses of mouse airway epithelial cells and alveolar macrophages to virulent and avirulent strains of influenza A virus. Viral Immunology 2011; 24: 77-88.
- Tate MD, Job ER, Brooks AG, Reading PC. Glycosylation of the hemagglutinin modulates the sensitivity of H3N2 influenza viruses to innate proteins in airway secretions and virulence in mice. Virology 2011; 413: 84-92.
- Tate MD, Ioannidis LJ, Croker B, Brown LE, Brooks AG, Reading PC. The role of neutrophils during mild and severe influenza virus infections of mice. PLoS One 2011; 6: e17618.
- Tate MD, Brooks AG, Reading PC. Specific sites of N-linked glycosylation on the hemagglutinin of H1N1 subtype influenza A virus determine sensitivity to inhibitors of the innate immune system and virulence in mice. Journal of Immunology 2011; 187: 1884-1894.
- Tate MD, Brooks AG, Reading PC. Inhibition of lectin-mediated innate host defences in vivo modulates disease severity during influenza virus infection. Immunol Cell Biol 2011; 89: 482-491.
- Tate, M. D., A. G. Brooks AG, and P. C. Reading PC. Receptor specificity of the influenza virus hemagglutinin modulates sensitivity to soluble collectins of the innate immune system and virulence in mice. Virology 2011; 413: 128-138.
- Tate, M. D., A. G. Brooks AG, and P. C. Reading PC. Correlation between sialic acid expression and infection of murine macrophages by different strains of influenza virus. Microbes Infect 2011; 13: 202-207.
- Patel O, Pellicci DG, Uldrich AP, Sullivan LC, Bhati M, McKnight M, Richardson SK, Howell AR, Mallevaey TJ, Zhang JR, Bedel RG, Besra GS, Brooks AG, Kjer-Nielsen L, McCluskey J, Porcelli SA, Gapin L, Rossjohn J, Godfrey DI. Vbeta2 natural killer T cell antigen receptor-mediated recognition of CD1d-glycolipid antigen. Proc Natl Acad Sci U S A 2011; 108: 19007-19012.
- Londrigan SL, Turville SG, Tate MD, Deng YM, Brooks AG, Reading PC. N-Linked Glycosylation Facilitates Sialic Acid-Independent Attachment and Entry of Influenza A Viruses into Cells Expressing DC-SIGN or L-SIGN. J Virol 2011; 85: 2990-3000.
- Lau LS, Fernandez Ruiz D, Davey GM, de Koning-Ward TF, Papenfuss AT, Carbone FR, Brooks AG, Crabb BS, Heath WR. Blood-Stage Plasmodium berghei Infection Generates a Potent, Specific CD8+ T-Cell Response Despite Residence Largely in Cells Lacking MHC I Processing Machinery. J Infect Dis. 2011; 204: 1989-96.
- Hofstetter AR, Sullivan LC, Lukacher AE, Brooks AG.
Diverse roles of non-diverse molecules: MHC class Ib molecules in host defense and control of autoimmunity.
Curr Opin Immunol 2011; 23: 104-110.
[C1] Impact factor 10.41 Citations 2 [R: 0, P:50, W:60]
- Gebhardt T, Whitney PG, Zaid A, Mackay LK, Brooks AG, Heath WR, Carbone FR, Mueller SN. Different patterns of peripheral migration by memory CD4+ and CD8+ T cells. Nature 2011; 477: 216-219.
- Wojtasiak M, Pickett DL, Tate MD, Londrigan SL, Bedoui S, Brooks AG, Reading PC. Depletion of Gr-1+, but not Ly6G+, immune cells exacerbates virus replication and disease in an intranasal model of herpes simplex virus type 1 infection. J Gen Virol 2010; 91: 2158-2166.
- Wojtasiak M, Pickett DL, Tate MD, Bedoui S, Job ER, Whitney PG, Brooks AG, Reading PC. Gr-1+ cells, but not neutrophils, limit virus replication and lesion development following flank infection of mice with herpes simplex virus type-1. Virology 2010; 407: 143-151.
- Walpole NG, L. Kjer-Nielsen L, Kostenko L, McCluskey J, Brooks AG, Rossjohn J, Clements CS. The structure and stability of the monomorphic HLA-G are influenced by the nature of the bound peptide. J Mol Biol 2010; 397: 467-480.
- Tate MD, Pickett DL, van Rooijen N, Brooks AG, Reading PC. Critical role of airway macrophages in modulating disease severity during influenza virus infection of mice. J Virol 2010; 84: 7569-7580.
- Tate MD, Brooks AG, Reading PC. Inhibition of lectin-mediated innate host defences in vivo modulates disease severity during influenza virus infection. Immunol Cell Biol 2010; 89: 482-91.
- Reading PC, Whitney PG, Pickett DL, Tate MD, and Brooks AG. Influenza viruses differ in ability to infect macrophages and to induce a local inflammatory response following intraperitoneal injection of mice. Immunol Cell Biol 2010; 88: 641-650.
- Meehan AC, Sullivan LC, Mifsud NA, Brooks AG, Snell GI, Kotsimbos TC, Westall GP. Natural killer cell activation in the lung allograft early posttransplantation. Transplantation 2010; 89: 756-763.
- Job ER, Deng YM, Tate MD, Bottazzi B, Crouch EC, Dean MM, Mantovani A, Brooks AG, Reading PC. Pandemic H1N1 influenza A viruses are resistant to the antiviral activities of innate immune proteins of the collectin and pentraxin superfamilies. J Immunol 2010; 185: 4284-4291.
- Gras S, Chen Z, Miles JJ, Liu YC, Bell MJ, Sullivan LC, Kjer-Nielsen L, Brennan RM, Burrows JM, Neller MA, Khanna R, Purcell AW, Brooks AG, McCluskey Rossjohn J, Burrows SR. Allelic polymorphism in the T cell receptor and its impact on immune responses. J Exp Med 2010; 207: 1555-1567.
- Tate MD, Deng YM, Jones JE, Anderson GP, Brooks AG, Reading PC. Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J Immunol 2009; 183: 7441-7450.
- Sexton A, Whitney PG, Chong SF, Zelikin AN, Johnston AP, De Rose R, Brooks AG , Caruso F, Kent SJ. A protective vaccine delivery system for in vivo T cell stimulation using nanoengineered polymer hydrogel capsules. ACS Nano 2009; 3: 3391-3400.
- Rose MJ, Brooks AG, Stewart LA, Nguyen TH, Schwarer AP. Killer Ig-like receptor ligand mismatch directs NK cell expansion in vitro. J Immunol 2009; 183: 4502-4508.
- Pellicci DG, Patel O, Kjer-Nielsen L, Pang SS, Sullivan LC, Kyparissoudis K, Brooks AG, Reid HH, Gras S, Lucet IS, Koh R, Smyth MJ, Mallevaey T, Matsuda JL, Gapin L, McCluskey J, Godfrey DI, Rossjohn J. Differential recognition of CD1d-alpha-galactosyl ceramide by the V beta 8.2 and V beta 7 semi-invariant NKT T cell receptors. Immunity 2009; 31: 47-59.
- Macdonald WA, Chen Z, Gras S, Archbold JK, Tynan FE, Clements CS, Bharadwaj M, Kjer-Nielsen L, Saunders PM, Wilce MC, Crawford F, Stadinsky B, Jackson D, Brooks AG, Purcell AW, Kappler JW, Burrows SR, Rossjohn J, McCluskey J. T cell allorecognition via molecular mimicry. Immunity 2009; 31: 897-908.
- Gras S, Burrows SR, Kjer-Nielsen L, Clements CS, Liu YC, Sullivan LC, Bell MJ, Brooks AG, Purcell AW, McCluskey Rossjohn J. The shaping of T cell receptor recognition by self-tolerance. Immunity 2009; 30: 193-203.
- Bedoui S, Whitney PG, Waithman J, Eidsmo L, Wakim L, Caminschi I, Allan RS,
Wojtasiak M, Shortman K, Carbone FR, Brooks* AG, Heath WR.
Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells.
Nat Immunol 2009; 10: 488-495.
* Joint Senior and Corresponding Author
- Tate MD, Brooks AG, Reading PC. The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice. Respir Res 2008; 9: 57.
- Sullivan LC, Clements CS, Rossjohn J, Brooks AG. The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity. Tissue Antigens 2008; 72: 415-24.
- Silva A, Andrews DM, Brooks AG, Smyth MJ, Hayakawa Y. .
Application of CD27 as a marker for distinguishing human NK cell subsets.
Int Immunol 2008; 20: 625-630.
[C1] Impact factor 4.02 Citations 19 [R: 5, P:20, W:20]
- Reading PC, Bozza S, Gilbertson B, Tate M, Moretti S, Job ER, Crouch EC, Brooks AG, Brown LE, Bottazzi B, Romani L, Mantovani A. Antiviral activity of the long chain pentraxin PTX3 against influenza viruses. J Immunol 2008; 180: 3391-3398.
- Petrie EJ, Clements CS, Lin J, Sullivan LC, Johnson D, Huyton T, Heroux A,
Hoare HL, Beddoe T, Reid HH, Wilce MC, Brooks* AG, Rossjohn J.
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence.
J Exp Med 2008; 205: 725-735.
* Joint Senior and Corresponding Author
- Westall GP, Brooks AG, Kotsimbos T. CD8+ T-cell maturation following lung transplantation: the differential impact of CMV and acute rejection. Transpl Immunol 2007; 18: 186-192.
- Sullivan LC, Clements CS, Beddoe T, Johnson D, Hoare HL, Lin J, Huyton T, Hopkins EJ, Reid HH, Wilce MC, Kabat J, Borrego F, Coligan JE, Rossjohn J, and Brooks AG. The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition. Immunity 2007; 27: 900-911.
- Hoare HL, Sullivan LC, Pietra G, Clements CS, Lee EJ, Ely LK, Beddoe T, Falco M, Kjer-Nielsen L, Reid HH, McCluskey J, Moretta L, Rossjohn J, Brooks AG. Structural basis for a major histocompatibility complex class Ib-restricted T cell response. Nat Immunol 2006; 7: 256-264.
- Coles RM, Mueller SN, Heath WR, Carbone FR, Brooks AG. Progression of armed CTL from draining lymph node to spleen shortly after localized infection with herpes simplex virus 1. J Immunol 2002; 168: 834-838.
- Boyington JC, Motyka SA, Schuck P, Brooks AG, Sun PD. Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand. Nature 2000; 405: 537-543.
- Borrego F, Ulbrecht M, Weiss EH, Coligan JE, Brooks AG. Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis. J Exp Med 1998; 187: 813-818.
- Brooks AG, Posch PE, Scorzelli CJ, Borrego F, Coligan JE. NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor. J Exp Med 1997; 185: 795-800.