Journal
INTERNATIONAL IMMUNOLOGY
Volume 12, Issue 11, Pages 1553-1560Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/12.11.1553
Keywords
autoimmunity; clonal expansion; experimental autoimmune encephalomyelitis; MHC class II tetramers; T lymphocytes
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Funding
- NIAID NIH HHS [R01 AI42929] Funding Source: Medline
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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 Map 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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