Pathways of Antigen Processing

Blum, Janice S.; Wearsch, Pamela A.; Cresswell, Peter

doi:10.1146/annurev-immunol-032712-095910

Cited by 1,265 publications

(1,165 citation statements)

References 232 publications

(225 reference statements)

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“…The resulting peptides are transported into the ER through the transporter associated with antigen processing (TAP), where they are loaded onto the awaiting MHC class I molecules by specialized chaperones (24)(25)(26). It is also suggested that some of the MHC peptides are produced by degradation of ER-resident proteins and their signal peptides (27,28).…”

Section: Dripome | Immunopeptidome | Dynamic Silacmentioning

confidence: 99%

The nature and extent of contributions by defective ribosome products to the HLA peptidome

Bourdetsky

Schmelzer

Admon

2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Rapid degradation of newly synthesized proteins, followed by presentation of the resulting peptides by the MHC molecules, serves as an early alert for the immune system during pathogen infection. This study defines the relative contribution to the MHC peptidome of defective ribosome products (DRiPs), which are newly synthesized and rapidly degraded proteins, vs. mature proteins, degraded at the end of their functional lifetimes (retirees). The rates of synthesis of the individual MHC peptides and their source proteins were followed using stable isotope labeling and quantitative proteomics and peptidomics analyses. We conclude that DRiPs are a significant source of MHC peptides. Many of these DRiPs are misassembled surplus subunits of protein complexes and therefore are degraded soon after synthesis.

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Section: Dripome | Immunopeptidome | Dynamic Silacmentioning

confidence: 99%

The nature and extent of contributions by defective ribosome products to the HLA peptidome

Bourdetsky

Schmelzer

Admon

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…2 This activity involves the degradation of foreign proteins (antigens) in endo-lysosomal compartments, binding of the resulting peptides to MHC II, and delivery of the MHC II-peptide complexes to the cell surface for presentation to helper T lymphocytes. 3 Material present in endosomal compartments including plasma membrane proteins, components of the endosomal route and extracellular pathogens that are captured by endocytosis is thus readily presented via MHC II. Autophagy enables cells to expand the repertoire of antigens presented via this pathway by delivering cytosolic material to endo-lysosomal compartments, where it can be used as a source of MHC II peptide ligands.…”

Section: Introductionmentioning

confidence: 99%

“…The MHC I-peptide complexes are delivered to the plasma membrane for activation of cytotoxic T lymphocytes. 3 Cross-presentation is carried out primarily, if not only, by specific types of dendritic cells (DC). DC are highly specialized cells of the immune system that are dedicated to surveillance of the extracellular environment, the capture of pathogens and the initiation of T cell immunity.…”

Section: Introductionmentioning

confidence: 99%

Differential use of autophagy by primary dendritic cells specialized in cross-presentation

et al. 2015

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Abbreviations: 3-MA, 3-methyladenine; Atg7-DC CKO, Atg7 DC conditional knockout; BafA, bafilomycin A 1 ; CD, cluster of differentiation; CTL, cytotoxic T lymphocyte; DC, dendritic cell; DALIS, dendritic cell aggresome-like inducible structures; green fluorescent protein, GFP; IFC imaging flow cytometry; LAP, LC3 associated phagocytosis; LC3B, microtubule-associated protein 1 light chain 3 b; MHC II, major histocompatibility complex class II; MHC I, major histocompatibility complex class I; OVA, ovalbumin; OT-I, OVA-specific CD8 C T cell; OT-II, OVA-specific CD4 C T cell; SIM, structured illumination microscopy.Antigen-presenting cells survey their environment and present captured antigens bound to major histocompatibility complex (MHC) molecules. Formation of MHC-antigen complexes occurs in specialized compartments where multiple protein trafficking routes, still incompletely understood, converge. Autophagy is a route that enables the presentation of cytosolic antigen by MHC class II molecules. Some reports also implicate autophagy in the presentation of extracellular, endocytosed antigen by MHC class I molecules, a pathway termed "cross-presentation." The role of autophagy in cross-presentation is controversial. This may be due to studies using different types of antigen presenting cells for which the use of autophagy is not well defined. Here we report that active use of autophagy is evident only in DC subtypes specialized in cross-presentation. However, the contribution of autophagy to cross-presentation varied depending on the form of antigen: it was negligible in the case of cell-associated antigen or antigen delivered via receptor-mediated endocytosis, but more prominent when the antigen was a soluble protein. These findings highlight the differential use of autophagy and its machinery by primary cells equipped with specific immune function, and prompt careful reassessment of the participation of this endocytic pathway in antigen cross-presentation.

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“…Contrary to immature DCs, activated DCs efficiently convert to stable expressors of newly formed pMHCII complexes at their plasma membrane to increase the chance of interaction with TCRs on CD4 þ T cells. The distinctive mechanisms and pathways for MHCI and MHCII antigen loading and trafficking have recently been compared in several excellent reviews (Neefjes et al 2011;Blum et al 2013;Mantegazza et al 2013). The present review focuses in depth on mechanisms and pathways that regulate and determine the expression of pMHCII complexes at the plasma membrane of DCs.…”

mentioning

confidence: 99%

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

Broeke

Wubbolts

Stoorvogel

2013

Cold Spring Harbor Perspectives in Biology

142

102

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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.

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Pathways of Antigen Processing

Cited by 1,265 publications

References 232 publications

The nature and extent of contributions by defective ribosome products to the HLA peptidome

The nature and extent of contributions by defective ribosome products to the HLA peptidome

Differential use of autophagy by primary dendritic cells specialized in cross-presentation

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

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