Cell https://doi.org/10.1016/j.cell.2018.08.011 (2018)

T cells display spontaneous autoproliferation in multiple sclerosis (MS), but the mechanistic details underpinning this phenomenon are unclear. In Cell, Martin and colleagues observe that B cells from patients with MS that express the disease-susceptibility allele HLA-DR15 can drive the autoproliferation of T cells in an antigen-presentation-dependent manner. This autoproliferation of T cells is not observed in other organ-specific autoimmune diseases tested—neither Crohn’s disease nor psoriasis. A peptide screen shows that the B cells of patients with MS present a brain-associated antigen, RASGRP2, to T cells and that this drives T cell activation and production of effector cytokines, especially IFN-γ. Analysis of the TCR repertoires of autoproliferating T cells shows that they are enriched in the brain lesions of patients with MS. These findings from human patients throw light on the mechanism of T cell autoproliferation and add further weight to the pathological role of B cells in MS.