Understanding the Mechanism of Epitope Spreading in Autoimmune Disorders

I recently made a switch in my Research Interest from Protein Chemistry and Proteomics to Autoimmunity. Can anyone explain the molecular mechanisms behind epitope spreading in autoimmune diseases? How does it progress from the initial autoantigen to other self-antigens? Additionally, what are the best experimental approaches to study this phenomenon in vitro and in vivo? My group will be studying the transient changes occurring in the phase of antigenic transformation from self to immunogenic.

How about checking the following approach which is classical but still might come handy

Co-culture of APCs and Autoreactive T Cells

  • Use naïve or primed T cells with DCs pulsed with defined autoantigens.
  • Monitor T cell activation to new epitopes over time via ELISPOT, flow cytometry (cytokine staining), or tetramer assays.

2. Peptide Libraries / Epitope Mapping

  • Use overlapping peptide libraries from suspected autoantigens to stimulate T or B cells. This has to be followed with detection of spreading by observing responses to non-priming peptides.
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