University of Otago

McLellan Lab Research

Research Overview

A central theme of the laboratory is the study of the cells and the molecules involved in antigen presentation during immune responses to infection, cancer and allogeneic transplants. We have made major contributions to the field of cellular adhesion and costimulation, as well to our understanding of the different roles of dendritic cell subsets in the immune response. A recent focus has been the biology of soluble MHC molecules, especially as diagnostic markers for renal transplant rejection, but also for their role as integral membrane proteins of exosomes.

Research Projects

 

  • B cell exosomes: biosynthesis and cellular targets (Funded by a University of Otago Research Grant, Lottery Health NZ and The Marsden Fund)
  • Soluble HLA-DR as biomarker for disease and renal transplant rejection (Funded by Lottery Health). 
  • Natural Killer (NK) as ‘helper cells’ in tumour immunity.
  • Targeting compounds to mycobacteria for diagnosis and cure (Funded by Lottery Health NZ)

Lab Members and Postgraduate Students

Sarah Saunderson, BBioMedSciHons 1st class, (Lottery Health NZ PhD student), Frazer Coutinho PGDipSci (MSc Student), Lane Black BSc (MSc student, University of Otago Masters Scholarship), Remy Muhsin BBioMedSci Hons 1st Class, (PhD student, University of Otago PhD Scholarship), Felicity Caldwell (BBioMedSci Hons), Megan Giliam BSc (MSc student, 2013-), Tanvi Damani BSc (CTCR-Summer Research Scholarship, MSc student 2013-),  Melanie Krause BSc, Intern student (University of Osnabruck), Sherry Lee (OMRF-Summer Research Scholarship) and Amy Dunn, BSc (Laboratory Manager).

Other Activities

Member of the Centre for Translational Cancer Research (Otago) and The Renal Theme (Otago). Former Manager, University of Otago Flow Cytometry Facility (2004-2012)

Collaborations

  • Prof. Paul Crocker (University of Dundee): Glycobiology of exosomes
  • Prof. Gregory Cook (Department of Microbiology): Biology of persister mycobacteria
  • Dr. Patrizia Stoitzner (University of Innsbruck): Dendritic cell and tumour biology
  • Prof. Norbert Koch (University of Bonn): HSV-1 interactions with the immune system / exosome biology / MHC-II structure and function.
  • Dr. Toby Coates (Queen Elizabeth Hospital, Adelaide), Dr. Hans-Peter Marti (Inselspital, Berne), Prof. Rob Walker (Dunedin Hospital): Detection of biomarkers for renal transplant rejection.
  • Garry Nixon (Department of Rural Health, University of Otago): anti-streptokinase antibodies present in NZ populations.

Sources of Funding

The group has recently received funding from The Marsden Fund, The William Sherriff Trust, Lottery Health, The University of Otago Research Grant committee and the Otago School of Medical Sciences.

Recent Publicity

Selected Publications

(See downloads section below for PDFs)

Bouwer AL, Saunderson SC, Dunn AC, Lester KL, Crowley LR, Jack RW,  McLellan AD. Rapid interferon-gamma release from natural killer cells induced by a streptococcal commensal. Journal of Interferon & Cytokine Research. In press

Czepluch W, Dunn AC, Everitt CL, Dorer D, Saunderson SC, Aldwell FE, McLellan AD. Extracellular forms of Mycobacterium bovis BCG in the mucosal lymphatic tissues following oral vaccination. Int. J. Mycobacteriology. In press. http://dx.doi.org/10.1016/j.ijmyco.2012.11.004

Ting YT, Coates PT, Walker RJ, McLellan AD. Urinary tubular biomarkers as potential early predictors of renal allograft rejection. Nephrology. 2012; 17(1):11-6.

Baker NJ, Schofield JC, Caswell MD, McLellan AD. An Investigation of Early Atipamezole Reversal of Medetomidine / Ketamine Anesthetised Mice. J. Am. Assoc. Lab. Anim. Sci. 2011; 50(6):916-20.

Nixon G, Blattner K, Dawson J, Dovey S, Black M, Wilkins G, Dunn AC, McLellan AD. Streptokinase antibodies in patients presenting with acute coronary syndrome in three rural New Zealand populations. Journal of Clinical Pathology 2011; 64(5):426-9.

Ting YT, Coates PT, Marti HP, Dunn AC, Parker RM, Pickering JW, Jack RW, Kemp RA, Walker RJ, McLellan AD. Urinary soluble HLA-DR is a potential biomarker for acute renal transplant rejection. Transplantation 2010; 89(9):1071-8.

Temme S, Eis-Hübinger A, McLellan AD, Koch N. The Herpes Simplex Virus-1 Encoded Glycoprotein B Diverts HLA-DR Into the Exosome Pathway. J. Immunol. 2010; 184: 236-43.

Stoitzner P, Romani N, McLellan AD, Tripp CH, Ebner S. Isolation of skin dendritic cells from mouse and man. Methods Mol Biol. 2010: 595:235-48.

Bouwer AL, Netter P, Kemp RA and McLellan AD. A defined serum-free medium useful for monitoring anti-melanoma responses induced by dendritic cell immunotherapy. J. Immunological Methods. 2009; 352: 178-181.

Ting YT, Temme S, Koch N, McLellan AD. A new monoclonal antibody recognizing a linear determinant on the HLA-DR-chain N-terminus. Hybridoma 2009; 28: 423-9.

McLellan AD. Exosome release by primary B cells. Critical Reviews in Immunology. 2009; 29(3) 203-217.

Gebhard S, Hümpel A, McLellan AD and Cook GM. The alternative sigma factor SigF of Mycobacterium smegmatis is required for survival of heat shock, acidic pH and oxidative stress. Microbiology-SGM. 2008; 154: 2786-95.

Saunderson SC, Schuberth PC, Miller, L, Hock, BD, Dunn, AC, MacKay, PA, Jack, RW, Koch N. and McLellan AD. Induction of exosome release in primary B cells stimulated via CD40 and the IL-4 receptor. Journal of Immunology. 2008; 180(12):8146- 52.

Koch N, McLellan AD, Neumann J. A revised model for invariant chain-mediated assembly of Major Histocompatibility Complex class II peptide receptors. Trends in Biochemical Sciences 2007; 32(12):532-7.

Dorer DE, Czepluch W, Lambeth MR, Dunn AC, Reitinger C, Aldwell FE, McLellan AD. Lymphatic tracing and T cell responses following oral vaccination with live Mycobacterium bovis (BCG). Cellular Microbiology. 2007; 9(2): 544-553.

O'Donnell J, Hayman M, Spellerberg M, McLellan AD; Brooksbank K, Chapman P, Stamp L. Antineutrophil cytoplasmic antibody measurement - advantages and disadvantages of a capture PR3 ELISA and a direct PR3 ELISA. Pathology 2007; 39(2):258-63.

MacKay PA, Leibundgut-Landmann S, Koch N, Dunn AC, Reith W, Jack RW, McLellan AD. Circulating, soluble forms of major histocompatability complex antigens are not exosome-associated. European Journal of Immunology 2006; 36(11):2875- 2884.

Douillard P, Stoitzner P, Tripp CH, Clair-Moninot V, Ait-Yahia S, McLellan AD, Eggert A, Romani N, and Saeland S. Mouse lymphoid tissue contains distinct subsets of langerin / CD207+ dendritic cells, only one of which represents epidermal-derived Langerhans cells. Journal of Investigative Dermatology. 2005; 125(5):983-94.

Aldwell FE, Baird MA, Fitzpatrick CE, McLellan AD., Cross F, Lambeth M, and Buchan GS Oral vaccination of mice with lipid-encapsulated Mycobacterium bovis BCG: Anatomical sites of bacterial replication and immune activity. Immunology and Cell Biology. 2005; 83(5):549-53.

Hock BD, Roberts G, McKenzie JL, Gokhale P, Salm N, McLellan AD, Patton N, Roake JA. Exposure to the electrofusion process can increase the immunogenicity of human cells. Cancer Immunology and Immunotherapy. 2005; 54:880-890.

Leverkus M, McLellan AD, Heldmann M, Eggert AO, Brocker EB, Koch N, Kampgen E. MHC class II-mediated apoptosis in dendritic cells: a role for membrane-associated and mitochondrial signaling pathways. Int Immunol. 2003; 15(8):993-1006.

Kammerer U, Eggert AO, Kapp M, McLellan AD, Geijtenbeek TB, Dietl J, VanKooyk Y, Kampgen E. Unique Appearance of Proliferating Antigen-Presenting Cells Expressing DC-SIGN(CD209) in the Decidua of Early Human Pregnancy. Am J Pathol. 2003; 162(3):887-96.

Stoitzner P, Holzmann S, McLellan AD, Ivarsson L, Stossel H, Kapp M,Kammerer U, Douillard P, Kampgen E, Koch F, Saeland S, Romani N. Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207. J Invest Dermatol. 2003; 120(2):266-74.

McLellan AD, Kapp M, Eggert A, Linden C, Bommhardt U, Brocker EB, Kammerer U, Kampgen E. Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression. Blood. 2002; 99(6):2084-93.

Kolb-Maurer A, Pilgrim S, Kampgen E, McLellan AD, Brocker EB, Goebel W,Gentschev I. Antibodies against listerial protein 60 act as an opsonin for phagocytosis of Listeria monocytogenes by human dendritic cells. Infect Immun. 2001; 69(5):3100-9.

Schrama D, thor Straten P, Fischer WH, McLellan AD, Brocker EB, Reisfeld RA, Becker JC. Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue. Immunity. 2001; 14(2):111-21.

McLellan AD, Terbeck G, Mengling T, Starling GC, Kiener PA, Gold R, Brocker EB, Leverkus M, Kampgen E. Differential susceptibility to CD95 (Apo-1/Fas) and MHC class II-induced apoptosis during murine dendritic cell development. Cell Death Differ. 2000; 7(10):933-8.

McLellan AD, Brocker EB, Kampgen E. Dendritic cell activation by danger and antigen-specific T-cell signalling. Exp Dermatol. 2000; 9(5):313-22.

McLellan A, Heldmann M, Terbeck G, Weih F, Linden C, Brocker EB, Leverkus M, Kampgen E. MHC class II and CD40 play opposing roles in dendritic cell survival. Eur J Immunol. 2000; 30(9):2612-9.

McLellan AD, Kampgen E. Functions of myeloid and lymphoid dendritic cells. Immunol Lett. 2000; 72(2):101-5.

McLellan AD, Heiser A, Hart DN. Induction of dendritic cell costimulator molecule expression is suppressed by T cells in the absence of antigen-specific signalling: role of cluster formation, CD40 and HLA-class II for dendritic cell activation. Immunology. 1999; 98(2):171-80.

McLellan AD, Heiser A, Sorg RV, Fearnley DB, Hart DN. Dermal dendritic cells associated with T lymphocytes in normal human skin display an activated phenotype. J Invest Dermatol. 1998; 111(5):841-9.

McLellan AD, Sorg RV, Williams LA, Hart DN. Human dendritic cells activate T lymphocytes via a CD40: CD40 ligand-dependent pathway. Eur J Immunol. 1996; 26(6):1204-10.

Starling GC, McLellan AD, Egner W, Sorg RV, Fawcett J, Simmons DL, Hart DN. Intercellular adhesion molecule-3 is the predominant co-stimulatory ligand for leukocyte function antigen-1 on human blood dendritic cells. Eur J Immunol. 1995;2 5(9):2528-32.

McLellan AD, Starling GC, Williams LA, Hock BD, Hart DN. Activation of human peripheral blood dendritic cells induces the CD86 co-stimulatory molecule. Eur J Immunol. 1995; 25(7):2064-8.

McLellan AD, Starling GC, Hart DN. Isolation of human blood dendritic cells by discontinuous Nycodenz gradient centrifugation. J Immunol Methods. 1995,184:81-9.

 

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