Figure 11.

Concept for T cell activation within the CLNs. (a) MOG draining via interstitial fluid (ISF) or cerebrospinal fluid (CSF) to the CLNs is captured by DC-like phagocytic cells (de Vos et al., 2002). (b, c) T cells against the two dominant epitopes (24–36 and 40–48) are probably not deleted during thymic negative selection as both epitopes are vulnerable to destruction by TSSP, which cleaves at SP/PP residues present in both epitopes (Serre et al., 2017). Processing of MOG in myeloid APCs and B cells is led by catG, which cleaves at arginine ($R$) residues (Jagessar et al., 2016). This mechanism prevents peripheral activation of autoaggressive T cells that have escaped thymic selection. (b) The peptide sequence left after cleavage of the MOG40-48 epitope at Arg${}^{\mathrm{41}}$ and Arg${}^{\mathrm{46}}$ (the 4-mer 42–45) is too short for filling the peptide-binding cleft of the MHC class I molecule. In the BLC, however, the MOG40-48 epitope is protected against destructive processing. (c) Cleavage of the MOG24-36 epitope at Arg${}^{\mathrm{25}}$ may have little effect as a peptide of sufficient length (the 9-mer 26–34) is left intact for filling the peptide-binding cleft of the MHC class II molecule.