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

Radu, Caius G., Anderton, Stephen M., Firan, Mihail, Wraith, David C. and Ward, E. Sally (2000) Detection of autoreactive T cells in H-2(u) mice using peptide-MHC multimers. International Immunology, 12 (11), 1553-1560. (doi:10.1093/intimm/12.11.1553).

Abstract

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-2(u) 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 T(h) 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-2(u) 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-A(u) 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.

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Contributors

Author: E. Sally Ward

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