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.
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.
Trollmo
C
C
Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Meyer
A L
AL
Steere
A C
AC
Hafler
D A
DA
Huber
B T
BT
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D002999:Clone Cells; D006801:Humans; D006825:Hybridomas; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology*; D022123:Lyme Disease Vaccines / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D010446:Peptide Fragments / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; D016169:Lymphocyte Function-Associated Antigen-1; C072045:OspA protein; D010446:Peptide Fragments