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

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.