| 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
(Affiliation: Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.)
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| Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 166
Issue 8
Pg. 5286-91
(Apr 15 2001)
ISSN: 0022-1767 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.)
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| Chemical References |
- Antigens, Surface
- Bacterial Outer Membrane Proteins
- Bacterial Vaccines
- Lipoproteins
- Lyme Disease Vaccines
- Lymphocyte Function-Associated Antigen-1
- OspA protein
- Peptide Fragments
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| 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)
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