MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

Abstract

For the initiation of adaptive immune responses, dendritic cells present antigenic peptides in association with major histocompatibility complex class II (MHCII) to naïve CD4 þ T lymphocytes. In this review, we discuss how antigen presentation is regulated through intracellular processing and trafficking of MHCII. Newly synthesized MHCII is chaperoned by the invariant chain to endosomes, where peptides from endocytosed pathogens can bind. In nonactivated dendritic cells, peptide-loaded MHCII is ubiquitinated and consequently sorted by the ESCRT machinery to intraluminal vesicles of multivesicular bodies, ultimately leading to lysosomal degradation. Ubiquitination of newly synthesized MHCII is blocked when dendritic cells are activated, now allowing its transfer to the cell surface. This mode of regulation for MHCII is a prime example of how molecular processing and sorting at multivesicular bodies can determine the expression of signaling receptors at the plasma membrane.

The activation of the adaptive immune system: Cross-talk between antigen-presenting cells, T cells and B cells

“…MHC class II processing is regulated by maturation stimuli in DCs. Whereas in immature DCs MHC class II continuously is recycled and degraded, upon maturation MHC class II is stabilized on the cell surface which allows for prolonged antigen presentation [24].…”

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

“…To demonstrate whether P. UF1-induced metabolites can prime Th17 cell differentiation, metabolomic analyses of P. UF1-gavaged H2-Ab1 -/-mice compared with H2-Ab1 -/-mice plus CD4 + T cells and PBS-gavaged H2-Ab1 -/-mice were performed. Data revealed different metabolic pathways, particularly in tryptophan and butanoate metabolism; however, no Th17 cells were promoted in the H2-Ab1 -/-mice lacking MHC II (Supplemental Figure 3, B and C), once again highlighting the critical role of MHC II in differential T cell activation (41). Furthermore, cytokines (e.g., IL-1β, IL-6) alone were not sufficient to induce Th17 cells in mice that were gavaged with the S-layer P. UF1, denoting that the S-layer and its deduced peptides are essential in Th17 cell differentiation (Supplemental Figure 3A).…”

Importance of Feedback and Feedforward Loops to Adaptive Immune Response Modeling

“…The detail on the mechanism of recognizing and presenting self vs. non‐self Ags is beyond the scope of this review and the reader is referred to refs. 23, 24, 25.…”