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

Myelin basic protein (MBP)-specific T cells play a critical role in the pat hogenesis of experimental autoimmune encephalomyelitis (EAE), a prototype f or 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 nonamer ic 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, u sing MHC class II tetramers, that 15,000-70,000 self-antigen-specific T-h c ells accumulate in the draining lymph nodes following immunization with spi nal cord homogenate or MBP1-9, In contrast, MBP1-9-specific T cells are und etectable 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 sug gest that the extremely low affinity of the N-terminal peptide for I-A(U) d oes not limit the MBP1-9-specific T cells from expanding into a sizeable po ol of autoreactive T cells, Therefore, the primary immune response to MBP1- 9 does not differ quantitatively from previously reported CD4(+) T cell res ponses to foreign antigens.