Size-based Sorting Of PinosomalLuminal Cargoes Contributes To Antigen Presentation

Unlike which of membrane-associated proteins, the delivery mechanism of endosomal luminal cargos is unclear. How the engulfed antigens, as luminal cargoes, are processed and transferred remains elusive. By chasing single microglial pinosomes with live-cell imaging and analyzing magnetically isolated pinosomes, we show here that small cargoes in pinosomal lumen are selectively delivered to lysosomes whereas large ones are retained. The size-based sorting is mediated by the kiss-and-run fusion between pinosomes and lysosomes, and inhibited by interfering with either the fission or fusion process. Engulfed proteins as natural antigens are hydrolyzed inside pinosomes and generated peptides are selectively delivered to MHC class II containing compartments. Inhibition of the size-based sorting reduces the efficiency of exogenous antigen presentation. Altogether, our study reveals a size-based sorting mechanism of pinosomal luminal cargoes, provides physiological relevance for the kiss-and-run fusion of intracellular organelles, and suggests a refined model for the processing and trafficking of exogenous antigens.