Project B01

Inter- and intramolecular cross-regulation during CNS autoimmunity

Background

During progression of autoimmune diseases, tissue injury may result in the release of sequestered autoantigens, which is believed to diversify the epitope specificity. The classical concept of epitope spreading assumes naïve T cells to recognize these ‘self’-determinants, yet the pool of such autoreactive cells is limited through tolerance mechanisms.

We hypothesize that during tissue-specific autoimmunity the de novo presentation of previously sequestered tissue-antigens preferentially recruits Treg cells rather than naïve T cells.

Strategy

We employ MHC class II tetramers to trace polyclonal populations of CNS-autoantigen-specific Treg cells and adoptive transfer models using TCR transgenic Treg cells of known antigen specificity.