RT Journal Article
SR Electronic
T1 Fast targeting of antigen and surface-derived MHCII into degradative compartments implies endosomal prewiring for antigen presentation in B cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 775882
DO 10.1101/775882
A1 S Hernández-Pérez
A1 M Vainio
A1 E Kuokkanen
A1 V Sustar
A1 J Rajala
A1 V Paavola
A1 P Petrov
A1 LO Awoniyi
A1 AV Sarapulov
A1 S Fórsten
A1 H Vihinen
A1 E Jokitalo
A1 A Bruckbauer
A1 PK Mattila
YR 2019
UL http://biorxiv.org/content/early/2019/10/01/775882.abstract
AB In order to mount high-affinity antibody responses, B cells internalise specific antigens and process them into peptides loaded onto MHCII for presentation to TH cells. While the biochemical principles of antigen processing and MHCII loading have been well dissected, how the endosomal vesicle system is wired to enable these specific functions remains much less studied. Here, we performed a systematic microscopy-based analysis of antigen trafficking in B cells to reveal its route to the MHCII peptide-loading compartment (MIIC). Surprisingly, we detected fast targeting of internalised antigen into peripheral acidic compartments that possessed the hallmarks of MIIC and also showed degradative capacity. In these vesicles, internalised antigen converged rapidly with membrane-derived MHCII and partially overlapped with Cathepsin-S and H2-M, both required for peptide loading. These early compartments appeared heterogenous and atypical as they contained a mixture of both early and late markers, indicating specialized endosomal route. Together, our data suggests that, in addition to previously-reported perinuclear late endosomal MIICs, antigen processing and peptide loading could start already in these specialized early peripheral acidic vesicles to support fast peptide-MHCII presentation.