{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:13:57Z","timestamp":1790396037068,"version":"4.1.0"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,10,10]]},"abstract":"<jats:p>\n                    We characterized antigen-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in six patients with treatment-resistant Lyme arthritis, using an HLA-DRB1*0401 major histocompatibility complex (MHC) class II tetramer covalently loaded with OspA\n                    <jats:sub>164\u2013175<\/jats:sub>\n                    , an immunodominant epitope of\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    . Direct analysis of OspA-tetramer binding CD4\n                    <jats:sup>+<\/jats:sup>\n                    cells in patients expressing the HLA-DRB1*0401 allele revealed frequencies of between &lt;0.005 and 0.1% in peripheral blood (\n                    <jats:italic>n<\/jats:italic>\n                    = 6), and between &lt;0.005 and 3.1% in synovial fluid (\n                    <jats:italic>n<\/jats:italic>\n                    = 3). OspA-tetramer\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    cells were directly cloned at 1 cell per well and expanded by mitogen and IL-2 on allogeneic feeder cells. As measured by [\n                    <jats:sup>3<\/jats:sup>\n                    H]thymidine incorporation, 95% of 168 T cell clones from synovial fluid binding the OspA-tetramer were antigen-reactive. Clones generated from peripheral blood revealed a different pattern of responsiveness when compared with clones generated from synovial fluid, as measured by proliferation, IFN-\u03b3, and IL-13 secretion. These clones, selected on the basis of their peptide binding, also responded to whole protein, but with a different cytokine profile. Our studies demonstrate that MHC class II tetramers can be used in humans to directly identify, isolate, and characterize antigen-reactive T cells from an inflammatory compartment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.190335897","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"11433-11438","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":118,"title":["Direct enumeration of\n                    <i>Borrelia<\/i>\n                    -reactive CD4 T cells\n                    <i>ex vivo<\/i>\n                    by using MHC class II tetramers"],"prefix":"10.1073","volume":"97","author":[{"given":"Abbie L.","family":"Meyer","sequence":"first","affiliation":[{"name":"Tufts University School of Medicine, Department of Pathology, Boston, MA 02111; Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; Howard Hughes Medical Institute, Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and Tufts University School of Medicine, Division of Rheumatology\/Immunology, New England Medical Center, Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Trollmo","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine, Department of Pathology, Boston, MA 02111; Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; Howard Hughes Medical Institute, Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and Tufts University School of Medicine, Division of Rheumatology\/Immunology, New England Medical Center, Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Crawford","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine, Department of Pathology, Boston, MA 02111; Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; Howard Hughes Medical Institute, Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and Tufts University School of Medicine, Division of Rheumatology\/Immunology, New England Medical Center, Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Marrack","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine, Department of Pathology, Boston, MA 02111; Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; Howard Hughes Medical Institute, Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and Tufts University School of Medicine, Division of Rheumatology\/Immunology, New England Medical Center, Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen C.","family":"Steere","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine, Department of Pathology, Boston, MA 02111; Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; Howard Hughes Medical Institute, Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and Tufts University School of Medicine, Division of Rheumatology\/Immunology, New England Medical Center, Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte T.","family":"Huber","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine, Department of Pathology, Boston, MA 02111; Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; Howard Hughes Medical Institute, Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and Tufts University School of Medicine, Division of Rheumatology\/Immunology, New England Medical Center, Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kappler","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine, Department of Pathology, Boston, MA 02111; Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; Howard Hughes Medical Institute, Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and Tufts University School of Medicine, Division of Rheumatology\/Immunology, New England Medical Center, Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Hafler","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine, Department of Pathology, Boston, MA 02111; Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; Howard Hughes Medical Institute, Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and Tufts University School of Medicine, Division of Rheumatology\/Immunology, New England Medical Center, Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,9,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80572-5"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5284.94"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8476"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.1.291"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80470-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.4049\/jimmunol.162.3.1765","volume":"162","author":"Bieganowska K","year":"1999","unstructured":"K Bieganowska, P Hollsberg, G J Buckle, D G Lim, T F Greten, J Schneck, J D Altman, S Jacobson, S L Ledis, B Hanchard, et al. 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