T Cells Specific for Post-translational Modifications Escape Intrathymic Tolerance Induction

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jan 26

PMID 29367624

Citations 50

Authors

Bruno Raposo

Patrick Merky

Christina Lundqvist

Hisakata Yamada

Vilma Urbonaviciute

Colin Niaudet

Johan Viljanen

Jan Kihlberg

Bruno Kyewski

Olov Ekwall

Rikard Holmdahl

Johan Backlund

Affiliations

Soon will be listed here.

Abstract

Establishing effective central tolerance requires the promiscuous expression of tissue-restricted antigens by medullary thymic epithelial cells. However, whether central tolerance also extends to post-translationally modified proteins is not clear. Here we show a mouse model of autoimmunity in which disease development is dependent on post-translational modification (PTM) of the tissue-restricted self-antigen collagen type II. T cells specific for the non-modified antigen undergo efficient central tolerance. By contrast, PTM-reactive T cells escape thymic selection, though the PTM variant constitutes the dominant form in the periphery. This finding implies that the PTM protein is absent in the thymus, or present at concentrations insufficient to induce negative selection of developing thymocytes and explains the lower level of tolerance induction against the PTM antigen. As the majority of self-antigens are post-translationally modified, these data raise the possibility that T cells specific for other self-antigens naturally subjected to PTM may escape central tolerance induction by a similar mechanism.

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