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A role for mitochondria in antigen processing and presentation
Author(s) -
Bonifaz Laura C.,
CervantesSilva Mariana P.,
OntiverosDotor Elizabeth,
LópezVillegas Edgar O.,
SánchezGarcía F. Javier
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12392
Subject(s) - antigen processing , antigen presentation , oligomycin , antigen , microbiology and biotechnology , antigen presenting cell , biology , immunological synapse , mitochondrion , immune system , major histocompatibility complex , t cell , mhc restriction , immunology , biochemistry , t cell receptor , atpase , enzyme
Summary 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 ( APC s) and T lymphocytes is a two‐way signalling process. However, the role of mitochondria in APC s during this process remains unknown. For APC s to be able to activate T lymphocytes, they must first engage in an antigen‐uptake, ‐processing and ‐presentation process. Here we show that hen egg white lysozyme ( HEL ) ‐loaded B lymphocytes, as a type of APC , undergo a small but significant mitochondrial depolarization by 1–2 hr following antigen exposure, suggesting an increase in their metabolic demands. Inhibition of ATP synthase (oligomycin) or mitochondrial Ca 2+ uniporter ( MCU ) (Ruthenium red) had no effect on antigen uptake. Therefore, antigen processing and antigen presentation were further analysed. 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, which endogenously express HEL and by B lymphocytes loaded with the HEL 48–62 peptide, although to a lesser extent. ATP synthase inhibition and MCU inhibition had a clear inhibitory effect on antigen processing ( DQ ‐ OVA ). Taken together these results suggest that ATP synthase and MCU are relevant for antigen processing and presentation. Finally, APC mitochondria were found to re‐organize towards the APC –T immune synapse.