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 peptideMHC multimers
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, MBP19. To date, the MBP19-specific T cell repertoire has not been analyzed in quantitative terms. In the present study we demonstrate, using MHC class II tetramers, that 15,00070,000 self-antigen-specific Th cells accumulate in the draining lymph nodes following immunization with spinal cord homogenate or MBP19. In contrast, MBP19-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 MBP19-specific T cells from expanding into a sizeable pool of autoreactive T cells. Therefore, the primary immune response to MBP19 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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