Dr John Altin, Scientist, Applications Development, Prognosys Biosciences, San Diego, CA, USA.
Helper T cells are required to marshal the activity of other immune cell types against pathogens, but also underlie the maladaptive reactions to innocuous non-self and self-antigens that are central to the etiologies of allergy and autoimmunity. Here, I present mouse strains bearing single nucleotide variants (SNVs) that dysregulate helper T cell activity and result in allergic or autoimmune pathology. Molecular and cellular characterization of these mouse strains is used to define three novel pathways by which helper T cell activity is regulated: (1) a cell-extrinsic anticipatory pathway mediated by Foxp3+ regulatory T cells and sensitive to inherited partial loss of signaling downstream of the T cell antigen receptor; (2) a cell-intrinsic feedback pathway regulated by Ndfip1, an adapter protein for E3 ubiquitin ligases; and (3) a cell-extrinsic feedback pathway mediated by differentiation of effector Th2 cells into a novel Th2 inhibitory ‘Th2i’ cell type. Finally, I will survey some emerging technologies for recording the enormous antigenic diversity of the adaptive immune response, with applications in the early detection of autoimmunity and cancer, and in the development of vaccines against pathogens.