HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Trollmo, C. Articles by Huber, B. T. Search for Related Content PubMed PubMed Citation Articles by Trollmo, C. Articles by Huber, B. T.

Molecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1_L Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells¹

Christina Trollmo^2,*, Abbie L. Meyer^2,, Allen C. Steere, David A. Hafler^* and Brigitte T. Huber^3,

^* Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; Department of Pathology, and Division of Rheumatology/Immunology, Tufts University School of Medicine, New England Medical Center, Boston, MA 02111

Antibiotic treatment-resistant Lyme arthritis is a chronic inflammatory joint disease that follows infection with Borrelia burgdorferi (Bb). A marked Ab and T cell response to Bb outer surface protein A (OspA) often develops during prolonged episodes of arthritis. Furthermore, cross-reaction between the bacterial OspA and human LFA-1_L at the T cell level and the inability to detect Bb in the joint implicate an autoimmune mechanism. To analyze the nature of response to OspA and LFA-1_L, we used OspA-specific T cell hybrids from DR4 transgenic mice, as well as cloned human cells specific for OspA_165–184, the immunodominant epitope, from five DRB1*0401⁺ patients, using OspA-MHC class II tetramers. Although OspA_165–184 stimulated nearly all OspA-specific human T cell clones tested to proliferate and secrete IFN- and IL-13, LFA-1_L326–345 stimulated 10% of these clones to proliferate and a greater percentage to secrete IL-13. Assays with LFA- or OspA-DR4 monomers revealed that higher concentrations of LFA-DR4 were needed to stimulate dual-reactive T cell hybrids. Our analysis at the clonal level demonstrates that human LFA-1_L326–345 behaves as a partial agonist, perhaps playing a role in perpetuating symptoms of arthritis.

This article has been cited by other articles:

				P. Kannian, E. E. Drouin, L. Glickstein, W. W. Kwok, G. T. Nepom, and A. C. Steere Decline in the Frequencies of Borrelia burgdorferi OspA161 175-Specific T Cells after Antibiotic Therapy in HLA-DRB1*0401-Positive Patients with Antibiotic-Responsive or Antibiotic-Refractory Lyme Arthritis J. Immunol., November 1, 2007; 179(9): 6336 - 6342. [Abstract] [Full Text] [PDF]

				C. Parra-Lopez, J. M. Calvo-Calle, T. O. Cameron, L. E. Vargas, L. M. Salazar, M. E. Patarroyo, E. Nardin, and L. J. Stern Major Histocompatibility Complex and T Cell Interactions of a Universal T Cell Epitope from Plasmodium falciparum Circumsporozoite Protein J. Biol. Chem., May 26, 2006; 281(21): 14907 - 14917. [Abstract] [Full Text] [PDF]

				A. C. Steere, W. Klitz, E. E. Drouin, B. A. Falk, W. W. Kwok, G. T. Nepom, and L. A. Baxter-Lowe Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide J. Exp. Med., April 17, 2006; 203(4): 961 - 971. [Abstract] [Full Text] [PDF]

				M. E. Aguero-Rosenfeld, G. Wang, I. Schwartz, and G. P. Wormser Diagnosis of Lyme Borreliosis Clin. Microbiol. Rev., July 1, 2005; 18(3): 484 - 509. [Abstract] [Full Text] [PDF]

				S. Ghosh, A. C. Steere, B. D. Stollar, and B. T. Huber In Situ Diversification of the Antibody Repertoire in Chronic Lyme Arthritis Synovium J. Immunol., March 1, 2005; 174(5): 2860 - 2869. [Abstract] [Full Text] [PDF]

				T. A. Willett, A. L. Meyer, E. L. Brown, and B. T. Huber An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope PNAS, February 3, 2004; 101(5): 1303 - 1308. [Abstract] [Full Text] [PDF]

				F. Goulhen, D. Grenier, and D. Mayrand ORAL MICROBIAL HEAT-SHOCK PROTEINS AND THEIR POTENTIAL CONTRIBUTIONS TO INFECTIONS Critical Reviews in Oral Biology & Medicine, November 1, 2003; 14(6): 399 - 412. [Abstract] [Full Text] [PDF]

				D. S. Pikas, E. L. Brown, S. Gurusiddappa, L. Y. Lee, Y. Xu, and M. Hook Decorin-binding Sites in the Adhesin DbpA from Borrelia burgdorferi: A SYNTHETIC PEPTIDE APPROACH J. Biol. Chem., August 15, 2003; 278(33): 30920 - 30926. [Abstract] [Full Text] [PDF]

				A. C. Steere Lyme Disease N. Engl. J. Med., July 12, 2001; 345(2): 115 - 125. [Full Text] [PDF]