Photo of David C. Parker, Ph.D.

David C. Parker Ph.D.

  • (503) 494-1498
    • Molecular Microbiology and Immunology Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

Dr. Parker’s laboratory is interested in the cell-surface molecules and intracellular signaling pathways which determine whether an encounter between helper T cells and B cells or other antigen presenting cells results in immunity or tolerance. In a simplified model of peripheral tolerance to self, we found that a signal through OX40 (CD134) blocks functional anergy in transferred T cells responding to transgenic or allogeneic antigens, drives the T cells to differentiate into cytokine-secreting effector cells and results in fatal acute graft versus host disease in unirradiated recipient animals. Current work is focused on the role of the alternative pathway of NFkB activation in that model.

In a second project, the lab is exploring the possibility that certain subsets of weakly autoreactive B cells play an essential role as antigen-presenting cells in inducing tolerance to self antigens in T cells. In a third project, we are exploring the "immunological synapse," the structure that forms in the contact zone between a T cell and an antigen presenting cell. We are examining the role of the synapse in the specific delivery of effector cytokines from T cells to antigen presenting cells, with an emphasis on the membrane-bound TNF family members, CD40L (CD154) and FasL. We are also exploring differences among T cell subsets in the structure of the synapse and the functional consequences of those differences.

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Education

  • Ph.D., University of California, Berkeley California 1971

Memberships and associations

  • American Association of ImmunologistsFederation of American ScientistsUnion of Concerned Scientists

Publications

  • "Despite disorganized synapse structure, Th2 cells maintain directional delivery of CD40L to antigen-presenting B cells." PLoS ONE In: , Vol. 12, No. 10, e0186573, 01.10.2017.
  • "CD40L is transferred to antigen-presenting B cells during delivery of T-cell help." European Journal of Immunology In: , Vol. 47, No. 1, 01.01.2017, p. 41-50.
  • "CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation." Journal of Immunology In: , Vol. 193, No. 12, 15.12.2014, p. 5894-5903.
  • "A cell-intrinsic requirement for NF-κB-inducing kinase in CD4 and CD8 T cell memory." Journal of Immunology In: , Vol. 191, No. 7, 01.10.2013, p. 3663-3672.
  • "The carrier effect and T cell/B cell cooperation in the antibody response." Journal of Immunology In: , Vol. 191, No. 5, 01.09.2013, p. 2025-2027.
  • "Peripheral CD4+ T-cell tolerance is induced in vivo by rare antigen-bearing B cells in follicular, marginal zone, and B-1 subsets." European Journal of Immunology In: , Vol. 43, No. 7, 07.2013, p. 1818-1827.
  • "B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells." International Immunology  In: , Vol. 25, No. 4, 04.2013, p. 259-269.
  • "Preformed CD40L is stored in Th1, Th2, Th17, and T follicular helper cells as well as CD4 +8 - thymocytes and invariant NKT cells but not in Treg cells." PLoS One In: , Vol. 7, No. 2, e31296, 21.02.2012.
  • "NF-κB-inducing kinase plays an essential T cell-intrinsic role in graft-versus-host disease and lethal autoimmunity in mice." Journal of Clinical Investigation In: , Vol. 121, No. 12, 01.12.2011, p. 4775-4786.
  • "Cyclosporine-resistant, Rab27a-independent mobilization of intracellular preformed CD40 ligand mediates antigen-specific T cell help in vitro." Journal of Immunology In: , Vol. 187, No. 2, 15.07.2011, p. 626-634.
  • "The 50th midwinter conference of immunologists at asilomar." Nature Immunology In: , Vol. 12, No. 7, 05.2011, p. 583-585.
  • "Diversity in immunological synapse structure." Immunology In: , Vol. 131, No. 4, 12.2010, p. 466-472.
  • "Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b." Journal of Immunology In: , Vol. 184, No. 7, 01.04.2010, p. 3598-3608.
  • "Th1 and Th2 cells form morphologically distinct immunological synapses." Journal of Immunology In: , Vol. 181, No. 1, 2008, p. 393-399.
  • "Preformed CD40 ligand exists in secretory lysosomes in effector and memory CD4+ T cells and is quickly expressed on the cell surface in an antigen-specific manner." Blood In: , Vol. 110, No. 7, 01.10.2007, p. 2520-2527.
  • "OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rβ2, or T-bet." Journal of Immunology In: , Vol. 178, No. 12, 15.06.2007, p. 7694-7702.
  • "B cells expressing a natural polyreactive autoantibody have a distinct phenotype and are overrepresented in immunoglobulin heavy chain transgenic mice." Journal of Immunology  In: , Vol. 177, No. 4, 15.08.2006, p. 2412-2422.
  • "OX40 (CD134) engagement drives differentiation of CD4+ T cells to effector cells." European Journal of Immunology In: , Vol. 36, No. 5, 05.2006, p. 1093-1103.
  • "Antigen-specific accumulation of naïve, memory and effector CD4 T cells during anterior uveitis monitored by intravital microscopy." Cellular Immunology In: , Vol. 239, No. 1, 01.2006, p. 49-60.
  • "MHC transfer from APC to T cells following antigen recognition." Critical Reviews in Immunology In: , Vol. 26, No. 1, 2006, p. 1-21.
  • "Regulation of the small GTPase Rap1 and extracellular signal-regulated kinases by the costimulatory molecule CTLA-4." Molecular and Cellular Biology  In: , Vol. 25, No. 10, 05.2005, p. 4117-4128.
  • "Peptide-specific intercellular transfer of MHC class II to CD4+ T cells directly from the immunological synapse upon cellular dissociation." Journal of Immunology In: , Vol. 174, No. 1, 01.01.2005, p. 80-89.
  • "APCs in the anterior uveal tract do not migrate to draining lymph nodes." Journal of Immunology In: , Vol. 172, No. 11, 01.06.2004, p. 6701-6708.
  • "A signal through OX40 (CD134) allows anergic, autoreactive T cells to acquire effector cell functions." Journal of Immunology In: , Vol. 172, No. 11, 01.06.2004, p. 6735-6743.
  • "Ectopic B-Raf expression enhances extracellular signal-regulated kinase (ERK) signaling in T cells and prevents antigen-presenting cell-induced anergy." Journal of Biological Chemistry  In: , Vol. 278, No. 38, 19.09.2003, p. 35940-35949.
  • "Immunohistology of antigen-presenting cells in vivo : A novel method for serial observation of fluorescently labeled cells." Investigative Ophthalmology and Visual Science In: , Vol. 44, No. 5, 01.05.2003, p. 2004-2009.
  • "Live-cell dynamics and the role of costimulation in immunological synapse formation." Journal of Immunology In: , Vol. 169, No. 11, 01.12.2002, p. 6092-6101.
  • "Resting B lymphocytes as APC for naive T lymphocytes : Dependence on CD40 ligand/CD40." Journal of Immunology In: , Vol. 164, No. 2, 15.01.2000, p. 688-697.
  • "Differential coupling of membrane Ig and CD40 to the extracellularly regulated kinase signaling pathway." Journal of Immunology In: , Vol. 160, No. 5, 01.03.1998, p. 2121-2129.
  • "Selection of antigen-specific T cells by a single IE(k) peptide combination." Journal of Experimental Medicine  In: , Vol. 186, No. 9, 03.11.1997, p. 1441-1450.

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