• van den Elzen, Peter

    Titles

    Investigator, BC Children's Hospital
    Hematopathologist and Medical Director of Diagnostic Immunology, BC Children's Hospital and BC Women's Hospital & Health Centre
    Assistant Professor, Department of Pathology, University of British Columbia

    Degrees / Designations
    MD
    Primary Area of Research
    Childhood Diseases
    Secondary Area(s) of Research
    Phone
    604-875-2345 ext. 7343
    Fax
    604-875-3479
    Lab Phone
    604 875-2000 ext. 5887
    Mailing Address

    BC Children's Research Institute
    Room A4-145
    950 West 28th Avenue
    Vancouver, BC V5Z 4H4

    Affiliate Websites
    Research Areas
    • Immunology and Autoimmune disease
    • Lipid antigen presentation and apolipoproteins
    • Immune monitoring, clinical immunology, flow cytometry
    Summary

    The Immune Response to Lipids
    Immune responses are initiated when T cells recognize antigens displayed by antigen presenting cells (APC).  Classically, T cell recognition is towards peptide antigens displayed on APC by MHC molecules. More recently, lipid antigens were found to be similarly displayed by the MHC-like molecule, CD1, and recognized by an unconventional class of T cells, including NKT cells.  We are interested in exploring the biology of lipid antigen recognition by T cells, and the role this has in a number of human diseases, including autoimmune diseases such as multiple sclerosis, diabetes and lupus, infectious diseases as well as inflammatory diseases such as atherosclerosis. 

    We have recently discovered a new role for the serum lipoprotein apoE in the immune response to lipid antigens.  We will continue to explore the role of apolipoproteins in lipid antigen presentation as this has particular relevance to diseases such as atherosclerosis and autoimmune disease.
    A major endeavor will be to identify lipid and glycolipid antigens that are presented by CD1 to T cells in various physiological settings and the role they play in disease.  This will involve screening of candidate lipid antigens, as well as discovery approaches to find novel lipid antigens from various biological sources (cells, tissues or blood).

    Current Projects

    Autoimmunity to lipid antigens: The role of CD1-restricted T cells and apolipoproteins
    We are exploring whether autoimmunity to self lipids plays a role in the pathophysiology of diseases such as multiple sclerosis, diabetes, lupus and atherosclerosis. This involves characterization of lipid-reactive T cells and anti-lipid antibodies from the peripheral blood or tissues of patients and in animal models of disease.

    In multiple sclerosis, the lipid-rich myelin sheath is a target of immune attack, and we are exploring whether this attack is directed at the lipid components of myelin and the role that lipid transport proteins such as apoE have in this recognition.

    In type 1 diabetes, autoimmunity is directed against pancreatic beta cells and a regulatory role exists for NKT cells, which recognize glycolipid antigens. We are working to determine the mechanism of this regulation and the role that lipid/glycolipid recognition has in this process.

    Lupus is also characterized by autoimmunity to self antigens, and this may include lipid antigens such as phospholipids and blood borne lipids found in lipoproteins.

    Atherosclerosis is the underlying cause of the highest number of deaths in the Western World, and the inflammatory process that causes it likely begins early in life, and is particularly a byproduct of diseases such as diabetes, lupus and arthritis.  Perturbations in blood lipids are a key feature of atherosclerosis, as is an inflammatory response in the walls of blood vessels.  Our work, which defines a pathway by which the immune system directly targets blood lipids, has important implications for the pathogenesis of atherosclerosis.  We are exploring whether serum lipids can be targeted in atherosclerosis and associated conditions.

    The discovery of lipid antigens that are targeted by the immune system will lead to lipid-based therapies which can alter the immune response.

    The role of NKT cells in the immune response
    An important subset of CD1 restricted T cells include “NKT” cells which recognize glycolipids presented by CD1d.  NKT cells have been shown to play many diverse roles in immunity from the regulation of autoimmune diseases such as type 1 diabetes to a pro-inflammatory role in diseases such as atherosclerosis.  We are studying the mechanisms by which NKT cells exert this control, from their effect on B cells in the production of antibodies, to their effect on classical T cell immunity mediated by CD4+ and CD8+ T cells.

    Clinical Interests

    • Transfusion Medicine 
    • Immune Monitoring
    • Flow Cytometry
    Selected Publications

    Apolipoprotein mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells. Allan LL, Hoefl K, Zheng DJ, Chung BK, Kozak FK, Tan R, van den Elzen P. Blood. 2009 Jul 20. [Epub ahead of print]

    Penitente R, Nicolò C, van den Elzen P, Di Sante G, Agrati C, Aloisi F, Sercarz EE, Ria F.: Administration of PLP139-151 primes T cells distinct from those spontaneously responsive in vitro to this antigen. J Immunol. 2008 May 15;180(10):6611-22.

    Menezes JS, van den Elzen P, Thornes J, Huffman D, Droin NM, Maverakis E, Sercarz EE. A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE. J Clin Invest. 2007 Aug;117(8):2176-85.

    Brigl M*, van den Elzen P*, Chen X*, Meyers JH, Wu D, Wong CH, Reddington F, Illarianov PA, Besra GS, Brenner MB, Gumperz JE.  Conserved and heterogeneous lipid antigen specificities of CD1d-restricted NKT cell receptors. J Immunol. 2006 Mar 15;176(6):3625-34. (*co-authors)

    van den Elzen P, Garg S, Leon L, Brigl M, Leadbetter EA, Gumperz JE, Dascher CC, Cheng TY, Sacks FM, Illarionov PA, Besra GS, Kent SC, Moody DB, Brenner MB. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature. 2005 Oct 6;437(7060):906-10.

    Hava DL, Brigl M, van den Elzen P, Zajonc DM, Wilson IA, Brenner MB. CD1 assembly and the formation of CD1-antigen complexes. Curr Opin Immunol. 2005 Feb;17(1):88-94. Review.

    van den Elzen P, Menezes JS, Ametani A, Maverakis E, Madakamutil L, Tang XL, Kumar V, Sercarz EE. Limited clonality in autoimmunity: drivers and regulators. Autoimmun Rev. 2004 Nov;3(7-8):524-9.

    Dorfman DM, van den Elzen P, Weng AP, Shahsafaei A, Glimcher LH. Differential expression of T-bet, a T-box transcription factor required for Th1 T-cell development, in peripheral T-cell lymphomas.
    Am J Clin Pathol. 2003 Dec;120(6):866-73.

    Maverakis E, Beech J, Stevens DB, Ametani A, Brossay L, van den Elzen P, Mendoza R, Thai Q, Macias LH, Ethell D, Campagnoni CW, Campagnoni AT, Sette A, Sercarz EE. Autoreactive T cells can be protected from tolerance induction through competition by flanking determinants for access to class II MHC. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5342-7

    Ria F, van den Elzen P, Madakamutil LT, Miller JE, Maverakis E, Sercarz EE. Molecular characterization of the T cell repertoire using immunoscope analysis and its possible implementation in clinical practice. Curr Mol Med. 2001 Jul;1(3):297-304. Review.

    Maverakis E, van den Elzen P, Sercarz EE. Self-reactive T cells and degeneracy of T cell recognition: evolving concepts-from sequence homology to shape mimicry and TCR flexibility. J Autoimmun. 2001 May;16(3):201-9. Review

    Wilson SS, van den Elzen P, Maverakis E, Beech JT, Braciak TA, Kumar V, Sercarz EE. Residual public repertoires to self. J Neuroim

    Grants
    Honours & Awards

    Michael Smith Foundation for Health Research 2007, Career Investigator Award 2007-2013
    Multiple Sclerosis Society of Canada, Career Development Award 2007-2010
    Child & Family Research Institute, Clinician-Scientist Award 2007-2012
    National Multiple Sclerosis Society, Career Transition Fellowship 2005-2010,
    Paul E. Strandjord Young Investigator Award 2005.  Academy of Clinical Laboratory Physicians and Scientists. 
    National Multiple Sclerosis Society. Postdoctoral Fellowship 2000-2001
    Multiple Sclerosis Society of Canada. Postdoctoral Fellowship 2000-2001

    Research Group Members
    • Lenka Allan, PhD
    • Dongjun Zhang, MD
    • Annelein Stax, PhD
    • Goichi Kageyama, MD, PhD
    • Naoki Kitano, B.Sc.