title: A Role For Mitochondria In Antigen Processing And Presentation.
abstract: Immune synapse formation is critical for T lymphocyte activation, and mitochondria have a role in this process, by localizing close to the immune synapse, regulating intracellular calcium concentration, and providing locally required ATP. The interaction between antigen presenting cells (APCs) and T lymphocytes is a two-way signaling process. However, the role of mitochondria in antigen presenting cells during this process remains unknown. For APCs to be able to activate T lymphocytes, they must first engage in an antigen-uptake, -processing, and -presentation process. Here we show that HEL-loaded B lymphocytes, as a type of APCs, undergo a small but significant mitochondrial depolarization by 1-2 h following antigen exposure thus suggesting an increase in their metabolic demands. Inhibition of ATP synthase (oligomycin) or mitochondrial Ca2+uniporter (MCU) (Ruthenium red) had no effect on antigen uptake. Therefore, antigen processing and antigen presentation were further analyzed. Oligomycin treatment reduced the amount of specific MHC-peptide complexes but not total MHC II on the cell membrane of B lymphocytes which correlated with a decrease in antigen presentation. However, oligomycin also reduced antigen presentation by B lymphocytes that endogenously express HEL and by B lymphocytes loaded with the HEL48-62peptide, although to a lesser extent. ATP synthase inhibition and MCU inhibition had a clear inhibitory effect on antigen processing (DQ-OVA). Taking together these results suggest that ATP synthase and MCU are relevant for antigen processing and presentation. Finally, APCs mitochondria were found to re-organize towards the APC-T immune synapse. This article is protected by copyright. All rights reserved.
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica, Hospital de especialidades, Instituto Mexicano del Seguro Social, México.
authors.forename: Lc
authors.initials: L
authors.lastname: Bonifaz
authors.forename: Mp
authors.initials: M
authors.lastname: Cervantes-Silva
authors.forename: E
authors.initials: E
authors.lastname: Ontiveros-Dotor
authors.forename: Eo
authors.initials: E
authors.lastname: López-Villegas
authors.forename: Fj
authors.initials: F
authors.lastname: Sánchez-García
keywords: Antigen presentation; Antigen processing; immune synapse; mitochondria