Molecular mimicry in Lyme arthritis demonstrated at the single cell level: LFA-1 alpha L is a partial agonist for outer surface protein A-reactive T cells.

Abstract

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-1alpha(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-1alpha(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-gamma and IL-13, LFA-1alpha(L326-345) stimulated approximately 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-1alpha(L326-345) behaves as a partial agonist, perhaps playing a role in perpetuating symptoms of arthritis.

• Authors: C Trollmo, A L Meyer, A C Steere, D A Hafler, B T Huber
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 166 Issue 8 Pg. 5286-91 (Apr 15 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11290815 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Surface
• Bacterial Outer Membrane Proteins
• Bacterial Vaccines
• Lipoproteins
• Lyme Disease Vaccines
• Lymphocyte Function-Associated Antigen-1
• OspA protein
• Peptide Fragments

Topics

• Animals
• Antigens, Surface (immunology, metabolism)
• Bacterial Outer Membrane Proteins (agonists, immunology, metabolism)
• Bacterial Vaccines
• Borrelia burgdorferi Group (immunology)
• Clone Cells
• Humans
• Hybridomas
• Lipoproteins
• Lyme Disease (immunology)
• Lyme Disease Vaccines (agonists, immunology, metabolism)
• Lymphocyte Activation (immunology)
• Lymphocyte Function-Associated Antigen-1 (immunology, metabolism)
• Mice
• Mice, Transgenic
• Molecular Mimicry
• Peptide Fragments (agonists, immunology, metabolism)
• T-Lymphocyte Subsets (immunology, microbiology)