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International Immunology, Vol. 12, No. 11, 1553-1560, November 2000
© 2000 Japanese Society for Immunology

Detection of autoreactive T cells in H-2u mice using peptide–MHC multimers

Caius G. Radu, Stephen M. Anderton1, Mihail Firan, David C. Wraith1 and E. Sally Ward

Center for Immunology and Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75235-8576, USA
1 Department of Pathology and Microbiology, University of Bristol, Bristol BS8 1TD, UK

Correspondence to: E. S. Ward

Myelin basic protein (MBP)-specific T cells play a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity. In PL/J and B10.PL mice (H-2u haplotype), the immunodominant epitope of MBP is represented by an N-terminal nonameric peptide, MBP1–9. To date, the MBP1–9-specific T cell repertoire has not been analyzed in quantitative terms. In the present study we demonstrate, using MHC class II tetramers, that 15,000–70,000 self-antigen-specific Th cells accumulate in the draining lymph nodes following immunization with spinal cord homogenate or MBP1–9. In contrast, MBP1–9-specific T cells are undetectable in unimmunized H-2u mice and represent >60% of the CD4 cells in naive mice transgenic for a TCR specific for this epitope. The results suggest that the extremely low affinity of the N-terminal peptide for I-Au does not limit the MBP1–9-specific T cells from expanding into a sizeable pool of autoreactive T cells. Therefore, the primary immune response to MBP1–9 does not differ quantitatively from previously reported CD4+ T cell responses to foreign antigens.

Keywords: autoimmunity, clonal expansion, experimental autoimmune encephalomyelitis, MHC class II tetramers, T lymphocytes

Transmitting editor: C. Martinez-A


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