Limited repertoire of HLA-DRB1*0401-restricted MBP111-129-specific T cells in HLA-DRB 1*0401 Tg mice and their pathogenic potential

Since myelin basic protein (MBP) 111-129 is an immunodominant epitope in humans carrying HLA-DRB1*0401, we investigated the encephalitogenic potential of HLA-DRB1*0401-restricted MBP111-129-specific T cells using HLA-DRB1*0401/DRA*0101 transgenic (Tg) mice. Although we could not detect the primary recall response to MBP111-129 peptide after immunization of HLA-DRB1*0401/ DRA*0101 Tg mice with human MBP, Vbeta10(+) and Vbeta2(+) HLA-DRB1*0401-restricted MBP111-129-specific T cells proliferated after restimulation of the lymph node cells with human MBP111-129 in vitro. The Vbeta2(+) T cell line recognized only human MBP111-129 in the context of HLA-DRB1*0401, while the Vbeta10(+) T cell line recognized both the human and murine MBP111-129 epitopes. Therefore, we examined the encephalitogenic potential of the Vbeta10(+) T cell line in HLA-DRB1*0401/DRA*0101 Tg mice by adoptive transfer experiments. The Vbeta10(+) T cell line induced mild EAE and inflammatory lesions were observed in the spinal cord and the brainstem. In the spinal cord, the inflammation was observed in the peripheral nerve roots as well as in the CNS. These data suggest the pathogenic potential of HLA-DRB1*0401-restricted MBP111-129-specific T cells in humans. Published by Elsevier B.V.