Dr Anthony Antoniou
Our research is focused on the biology of the Major Histocompatibility Complex (MHC) Class I molecule HLA-B27. MHC class I molecules function to present peptides primarily derived from endogenous proteins to cytotoxic T cells at the cell surface and act as ligands for Natural Killer cells. MHC class I molecules assembly and acquire peptide within the lumen of the endoplasmic reticulum.
HLA-B27 exhibits a strong association with the inflammatory arthritic disorder, Ankylosing Spondylitis (AS). Approx. 95% of AS patients express HLA-B27. Many theories have been proposed to explain the role of HLA-B27 in the disease process. My lab is investigating the unusual biochemistry of HLA-B27 and trying to determine whether the biochemical characteristics exhibited by HLA-B27 could explain the association with AS.
The lab is especially interested in the enhanced propensity for HLA-B27 to misfold and in defining the consequences of misfolding. Recently, toxicity caused by protein misfolding has been linked to pathogenesis in a variety of diseases such as cystic fibrosis and Alzheimers disease, by inducing the unfolded protein response (UPR). It is possible that HLA-B27 misfolding could similarly induce the UPR. The lab is therefore investigating how HLA-B27 misfolds, folds and traffics within the cell. Furthermore, we would like to determine whether pharmacological therapies employed in misfolding diseases can target HLA-B27 misfoldin with the ultimate aim to be employed as a therapy in AS.
HLA-B27 also exhibits a strong association with another inflammatory arthritic disorder referred to as Reactive Arthritis (ReA). This arthritic condition follows infections by bacteria such as Salmonella and Campylobacter. The lab, in collaboration with Dr. Noursadeghi, Dr. Bajaj-Elliott and Dr. Dorrell (LSHTM) is interested in trying to understand the relationship between Salmonella/Campylobacter and HLA-B27 both at the cellular and biochemical level.
As well as HLA-B27, the lab is also investigating the folding of MHC class I molecules and how ER resident chaperones aid in this process, in particular the oxidoreductase ERp57, calnexin and BiP.
The lab also has a general interest in investigating how viral gene products can interfere and inhibit MHC class I molecule expression. We currently have interests in the role of Human Immunodeficiency Virus (HIV) accessory proteins such as Vpu and Nef in this process, the human cytomegalovirus (HCMV) genes US2 and US11 and the Kaposis sarcoma-associated herpes virus (KSHV) products K3 and K5.
MHC Class I Biology and Inflammatory Arthritis
Together with Dr Claudia Mauri, we organise two of the core modules for the Intercalated BSc in Immunology and Cell Pathology. For IMMN3008, we have developed the course content, with the emphasis of not only understanding basic immunological concepts but introducing current cutting edge research, techniques and methodologies used in the field of immunology. To enable the course to keep up to date with recent research , the course is taught by several lectures that active in several areas of the field of immunology. We have taken over the organisation of IMMN3009 from Prof. David Katz. This course aims to give a more in depth understanding of the inflammatory process to the development of the adaptive immune response. This course is taught by lecturers who specialise in the taught subject matter. I also participate in tutorials for some of the undergraduate immunology courses. I supervise students doing their research projects as part of the intercalated course and Masters students.
- Guililano DB, Fussell H, Lenart I, Tsao E, Nesbeth D, Fletcher AJ, Campbell E, Yousef N, Hebert DN, Gould K, Powis SJ, Antoniou AN (2013). Degradation of HLA-B27 dimers is mediated by EDEM in an ER stress regulated pathway.
- Guiliano DB, Antoniou AN (2013). Measuring synthesis and degradation of MHC class I molecules.. Methods Mol Biol, 960, 93 - 108. doi:10.1007/978-1-62703-218-6_8
- Giles J, Shaw J, Piper C, Wong-Baeza I, McHugh K, Ridley A, Li D, Lenart I, Antoniou AN, DiGleria K, Kuroki K, Maenaka K, Bowness P, Kollnberger S (2012). HLA-B27 homodimers and free H chains are stronger ligands for leukocyte Ig-like receptor B2 than classical HLA class I.. J Immunol, 188(12), 6184 - 6193. doi:10.4049/jimmunol.1102711
- Campbell EC, Antoniou AN, Powis SJ (2012). The multi-faceted nature of HLA class I dimer molecules.. Immunology, 136(4), 380 - 384. doi:10.1111/j.1365-2567.2012.03593.x
- Guiliano DB, Lenart I, Evans R, Iwawaki T, Acord J, Noursadeghi M, Nesbeth D, Campbell EC, Gould K, Powis SJ, Antoniou AN (2012). HLA-B27 MISFOLDING AND CELLULAR STRESS INFLUENCE THE LIFECYCLE OF INFECTING SALMONELLA? A POTENTIAL MECHANISM FOR SALMONELLA SURVIVAL IN REACTIVE ARTHRITIS PATIENTS?. CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 30(4), 637 - 637.
- Guiliano DB, Fussell H, Lenart I, Tsao E, Nesbeth D, Fletcher A, Campbell EC, Cameron A, Kellam P, Hebert DN, Gould K, Powis SJ, Antoniou AN (2012). HLA-B27 DIMERS ARE TARGETED FOR DEGRADATION BY AN ENDOPLASMIC RETICULUM STRESS INDUCED DEGRADATION PATHWAY - A POTENTIAL NOVEL THERAPEUTIC TARGET?. CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 30(4), 603 - 603.
- Lenart I, Guiliano DB, Burn G, Campbell EC, Morley KD, Fussell H, Powis SJ, Antoniou AN (2012). The MHC Class I heavy chain structurally conserved cysteines 101 and 164 participate in HLA-B27 dimer formation.. Antioxid Redox Signal, 16(1), 33 - 43. doi:10.1089/ars.2010.3693
- Antoniou AN, Lenart I, Guiliano DB (2011). Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules.. Int J Rheumatol, 2011, 486856 - . doi:10.1155/2011/486856
- Kotsiou E, Brzostek J, Lenart I, Antoniou AN, Dyson J, Gould KG (2011). Dimerization of soluble disulfide trap single-chain major histocompatibility complex class I molecules dependent on peptide binding affinity.. Antioxid Redox Signal, 15(3), 635 - 644. doi:10.1089/ars.2010.3691
- Antoniou AN, Guiliano D, Lenart I, North H, Nesbeth D, Gould K, Powis S (2011). Does the build up of molecular garbage lead to inflammatory arthritis?.
- Antoniou AN, Guiliano DB, Lenart I, Burn G, Powis SJ (2011). The oxidative folding and misfolding of human leukocyte antigen-b27.. Antioxid Redox Signal, 15(3), 669 - 684. doi:10.1089/ars.2010.3692
- Garstka MA, Fritzsche S, Lenart I, Hein Z, Jankevicius G, Boyle LH, Elliott T, Trowsdale J, Antoniou AN, Zacharias M, Springer S (2011). Tapasin dependence of major histocompatibility complex class I molecules correlates with their conformational flexibility.. FASEB J, 25(11), 3989 - 3998. doi:10.1096/fj.11-190249
- Guiliano DB, Nesbeth D, Gould K, Noursadeghi M, Antoniou AN (2010). The folding status of HLA-B27 influences the outcome S. typhimurium infection.
- Lynch S, Santos SG, Campbell EC, Nimmo AM, Botting C, Prescott A, Antoniou AN, Powis SJ (2009). Novel MHC class I structures on exosomes.. J Immunol, 183(3), 1884 - 1891. doi:10.4049/jimmunol.0900798
- Fussell H, Lenart I, Nesbeth D, Guiliano D, Gould K, Powis S, Antoniou AN (2009). HLA-B27 misfolding and dimerisation. doi:10.1016/j.cbpa.2009.04.327
- Powis SJ, Nesbeth D, Lenart I, Fussell H, Lamb T, Gould K, Antoniou AN (2009). Rapid acidification and alkylation: redox analysis of the MHC class I pathway.. J Immunol Methods, 340(1), 81 - 85. doi:10.1016/j.jim.2008.09.006
- Howe C, Garstka M, Al-Balushi M, Ghanem E, Antoniou AN, Fritzsche S, Jankevicius G, Kontouli N, Schneeweiss C, Williams A, Elliott T, Springer S (2009). Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class I molecules.. EMBO J, 28(23), 3730 - 3744. doi:10.1038/emboj.2009.296
- Powis SJ, Santos SG, Antoniou AN (2009). Biochemical features of HLA-B27 and antigen processing.. Adv Exp Med Biol, 649, 210 - 216.
- Santos SG, Lynch S, Campbell EC, Antoniou AN, Powis SJ (2008). Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells.. Arthritis Res Ther, 10(4), R100 - . doi:10.1186/ar2492
- Antoniou AN, Powis SJ (2008). Pathogen evasion strategies for the major histocompatibility complex class I assembly pathway.. Immunology, 124(1), 1 - 12. doi:10.1111/j.1365-2567.2008.02804.x
- Fussell H, Nesbeth D, Lenart I, Campbell EC, Lynch S, Santos S, Gould K, Powis SJ, Antoniou AN (2008). Novel detection of in vivo HLA-B27 conformations correlates with ankylosing spondylitis association.. Arthritis Rheum, 58(11), 3419 - 3424. doi:10.1002/art.23990
- Santos SG, Campbell EC, Lynch S, Wong V, Antoniou AN, Powis SJ (2007). Major histocompatability complex class 1-ERp57-tapasin interactions within the peptide-loading complex.. Journal of Biological Chemistry, 282(24), 17587 - 17593. doi:10.1074/jbc.M702212200
- Antoniou AN, Santos SG, Campbell EC, Lynch S, Arosa FA, Powis SJ (2007). ERp57 interacts with conserved cysteine residues in the MHC class I peptide-binding groove.. FEBS Lett, 581(10), 1988 - 1992. doi:10.1016/j.febslet.2007.04.034
- Beynon-Jones SM, Antoniou AN, Powis SJ (2006). Mutational analysis of the oxidoreductase ERp57 reveals the importance of the two central residues in the redox motif.. FEBS Lett, 580(7), 1897 - 1902. doi:10.1016/j.febslet.2006.02.055
- Santos SG, Antoniou AN, Sampaio P, Powis SJ, Arosa FA (2006). Lack of tyrosine 320 impairs spontaneous endocytosis and enhances release of HLA-B27 molecules. The Journal of Immunology, 176(5), 2942 - 2949.
- Antoniou AN, Ford S, Taurog JD, Butcher GW, Powis SJ (2004). Formation of HLA-B27 homodimers and their relationship to assembly kinetics. Journal of Biological Chemistry, 279(10), 8895 - 8902. doi:10.1074/jbc.M311757200
- Antoniou AN, Powis SJ, Elliott T (2003). Assembly and export of MHC class I peptide ligands.. Curr Opin Immunol, 15(1), 75 - 81.
- Li DN, Matthews SP, Antoniou AN, Mazzeo D, Watts C (2003). Multistep autoactivation of asparaginyl endopeptidase in vitro and in vivo.. J Biol Chem, 278(40), 38980 - 38990. doi:10.1074/jbc.M305930200
- Antoniou AN, Powis SJ (2003). Characterization of the ERp57-Tapasin complex by rapid cellular acidification and thiol modification.. Antioxid Redox Signal, 5(4), 375 - 379. doi:10.1089/152308603768295104
- Antoniou AN, Watts C (2002). Antibody modulation of antigen presentation: positive and negative effects on presentation of the tetanus toxin antigen via the murine B cell isoform of FcgammaRII.. Eur J Immunol, 32(2), 530 - 540. doi:10.1002/1521-4141(200202)32:2<530::AID-IMMU530>3.0.CO;2-X
- Antoniou AN, Ford S, Alphey M, Osborne A, Elliott T, Powis SJ (2002). The oxidoreductase ERp57 efficiently reduces partially folded in preference to fully folded MHC class 1 molecules. The EMBO Journal, 21(11), 2655 - 2663. doi:10.1093/emboj/21.11.2655
- Antoniou AN, Ford S, Pilley ES, Blake N, Powis SJ (2002). Interactions formed by individually expressed TAP1 and TAP2 polypeptide subunits.. Immunology, 106(2), 182 - 189.
- Antoniou AN, Moore N, Dyson PJ (2002). Remodelling of the S3 PA700 proteasome activator gene chromatin structure during thymocyte differentiation.. Immunogenetics, 54(4), 260 - 267. doi:10.1007/s00251-002-0475-3
- Antoniou AN, Blackwood SL, Mazzeo D, Watts C (2000). Control of antigen presentation by a single protease cleavage site.. Immunity, 12(4), 391 - 398.
- West MA, Antoniou AN, Prescott AR, Azuma T, Kwiatkowski DJ, Watts C (1999). Membrane ruffling, macropinocytosis and antigen presentation in the absence of gelsolin in murine dendritic cells.. Eur J Immunol, 29(11), 3450 - 3455. doi:10.1002/(SICI)1521-4141(199911)29:11<3450::AID-IMMU3450>3.0.CO;2-A
- Dyson PJ, Elliott J, Antoniou AN, Corley KT (1998). Efficient presentation of endogenous superantigen by H-2Aq.. Eur J Immunol, 28(3), 1034 - 1039. doi:10.1002/(SICI)1521-4141(199803)28:03<1034::AID-IMMU1034>3.0.CO;2-O
- Antoniou AN, Elliott J, Rosmarakis E, Dyson PJ (1998). MHC class II Ab diabetogenic residue 57 Asp/non-Asp dimorphism influences T-cell recognition and selection.. Immunogenetics, 47(3), 218 - 225.
- Hederer RA, Chandler PR, Dyson PJ, Antoniou AN, Millrain MM, Mellor AL, Simpson E, Robinson PJ (1996). Acceptance of skin grafts between mice bearing different allelic forms of beta 2-microglobulin.. Transplantation, 61(2), 299 - 304.