Mechanisms of MHC class I‐restricted antigen processing and cross‐presentation

Abstract

In this review, we discuss recent data from our laboratory that address two aspects of major histocompatibility complex (MHC) class I-restricted antigen processing. First, we consider the nature of the peptide-loading complex, which is the assembly of proteins in the endoplasmic reticulum (ER) into which newly synthesized MHC class I-beta(2) microglobulin (beta(2)m) heterodimers are incorporated, and the mechanisms involved in MHC class I assembly and peptide loading that are facilitated by the peptide-loading complex. Second, we discuss mechanisms of cross-presentation, the phenomenon whereby extracellular and luminal protein antigens can be processed by antigen-presenting cells, particularly dendritic cells, and presented by MHC class I molecules to CD8(+) T cells. The focus of the discussion is mainly on the human MHC class I system.

Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry*

“…MHC-associated peptides are recognized by T lymphocytes that are in turn activated to eliminate abnormal cells such as pathogen-infected and cancer cells. These immune peptides are divided in two classes: MHC class I and class II peptides that are distinguishable by (1) their structure, (2) the intracellular pathways by which they are generated, and (3) the type of T lymphocytes that recognize them, reviewed in (12,13). In brief, MHC class I peptides are predominantly 9 -12 amino acids in length or slightly longer (14 -17).…”

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

“…In contrast to MHCII, MHCI is expressed by nearly all cell types, and in nonprofessional antigen-presenting cells is exclusively loaded with peptides that are generated from cytosolic proteins by the ubiquitin/proteasome system. Cytosolic peptides can be translocated into the lumen of the endoplasmic reticulum (ER) for loading onto MHCI with the help of a dedicated peptideloading complex (Cresswell et al 2005). Peptide-loaded MHCI is then transported out of the ER via the Golgi apparatus to the plasma membrane, where it is stably exposed.…”

Peptide transporter TAP mediates between competing antigen sources generating distinct surface MHC class I peptide repertoires

“…Therefore, the process of MHC-I antigen processing and presentation, which operates in all nucleated cells of our body, is crucial for CTL immune surveillance [1][2][3]. The highly complex repertoire of MHC-I presented peptides reflects the total proteome of cells and derives from the physiological turnover of proteins, a process that is largely operated by the multicatalytic enzyme proteasome [4,5]. In addition to the proteasome, other proteolytic enzymes in the cytosol have been implicated in the liberation of peptides for MHC-I presentation, some of which can compensate for the lack of proteasome activity [1,6,7].…”