title: Indoctrinating T cells to attack pathogens through homeschooling.
abstract: Adaptive immunity is predicated on the ability of the T cell repertoire to have pre-existing specificity for the universe of potential pathogens. Recent findings suggest that T cell receptor (TCR)-self-major histocompatibility protein (pMHC) interactions limit autoimmune responses while enhancing T cell response to foreign antigens. We review these findings here, placing them in context of the current understanding of how TCR-self-pMHC interactions regulate T cell activation thresholds, and suggest that TCR-self-pMHC interactions increase the efficiency of the T cell repertoire by giving a competitive advantage to peptide cross-reactive T cells. We propose that self-reactivity and peptide cross-reactivity are controlled by particular CDR3 sequence motifs, which would allow thymic selection to contribute to solving the feat of broad pathogen specificity by exporting T cells that are pre-screened by positive and negative selection for the ability to be 'moderately' peptide cross-reactive.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Caitlin S
authors.initials: CS
authors.lastname: Parello
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: Eric.Huseby@umassmed.edu.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Huseby
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D010455:Peptides; D011948:Receptors, Antigen, T-Cell
keywords: CD5; T cell development; T cell homeostasis; TCR specificity; autoimmunity; dynamic tuning