Internalization and presentation of myelin antigens by the brain endothelium guides antigen-specific T cell migration

Melissa Lopes Pinheiro, Alwin Kamermans, Juan J. Garcia-Vallejo, Bert van het Hof, Laura Wierts, Tom O'Toole, Daniel Boeve, Marleen Verstege, Susanne M. A. van der Pol, Yvette Van Kooyk, Helga E. de Vries, Wendy W. J. Unger

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Trafficking of myelin-reactive CD4+ T-cells across the brain endothelium, an essential step in the pathogenesis of multiple sclerosis (MS), is suggested to be an antigen-specific process, yet which cells provide this signal is unknown. Here we provide direct evidence that under inflammatory conditions, brain endothelial cells (BECs) stimulate the migration of myelin-reactive CD4+ T-cells by acting as non-professional antigen presenting cells through the processing and presentation of myelin-derived antigens in MHC-II. Inflamed BECs internalized myelin, which was routed to endo-lysosomal compartment for processing in a time-dependent manner. Moreover, myelin/MHC-II complexes on inflamed BECs stimulated the trans-endothelial migration of myelin-reactive Th1 and Th17 2D2 cells, while control antigen loaded BECs did not stimulate T-cell migration. Furthermore, blocking the interaction between myelin/MHC-II complexes and myelin-reactive T-cells prevented T-cell transmigration. These results demonstrate that endothelial cells derived from the brain are capable of enhancing antigen-specific T cell recruitment.
Original languageEnglish
Article numbere13149
JournaleLife
Volume5
DOIs
Publication statusPublished - 23 Jun 2016

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