Identifying environmental antigens that activate myelin-specific T cells

Abstract

Human genetic and environmental factors underlie susceptibility to the T cell-mediated autoimmune disease, multiple sclerosis (MS). How the environment influences the pathogenesis of MS has been difficult to parse. A recent paper in Cell shows that environmental antigens that activate myelin-specific T cells can be identified with unprecedented accuracy.

Figure 1

Experimental flow path for identifying environmental antigens that active myelin-specific T cells. (A) Fully randomized HLA-DR15-peptide libraries are created in yeast, (B) probed with fluorescently-labeled TCR multimers and TCR-bound yeast are sorted and sequenced to identify critical TCR and MHC binding residues. (C) 2^nd generation HLA-DR15-peptide libraries are created that incorporate the critical TCR binding (red) and MHC binding (green) residues, stained with TCR multimers, sorted and sequenced, allowing for the characterization of peptide positions that modify TCR recognition (blue). (D) Peptide sequence information from the 2^nd generation library screen is used to create peptide search algorithms to identify potential antigens, and candidate antigens are validated.