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Antigen Processing and Presentation


Figure1. Antigen processing and presentation.

Introduction

Antigen presentation in an organism is accomplished by antigen-presenting cells (APC). Antigen-presenting cells are a kind of cells capable of processing antigens and presenting antigen peptides to T cells in the form of antigen peptide-MHC molecular complexes, and play an important role in immune recognition, immune response and immune regulation of the body.

The process of antigen processing and presentation mainly involves two processes. The first is antigen processing, which means that APC degrades and processes the exogenous antigen or the endogenous antigen produced by cytoplasm itself to a polypeptide fragment of a certain size, so that the antigen peptide is suitable for binding to the MHC molecule, and the complex is combined. Finally, the complex can be transported to the cell surface. The process is called antigen processing. Followed by antigen presentation, the antigen peptide-MHC molecular complex expressed on the surface of APC is recognized by T cells, thereby presenting antigen peptides to T cells and inducing T cell activation. Since T cells can only recognize antigenic peptides presented by APC, antigen processing and presentation play an important role in immune responses, especially cellular immunity.

Classes and function

APC

From the previous introduction, we know that the presentation of antigens is done by antigen-presenting cells. Depending on the source of the presented antigen and MHC molecule, antigen-presenting cells can be divided into two categories: 1. APCs present exogenous antigens by MHC classⅡmolecules. 2. APCs present endogenous antigens by MHC classⅠmolecules. The former APC can take up, process exogenous antigens and present antigen peptides to CD4+ T cells in the form of antigen peptide-MHC classⅡmolecular complexes. Both dendritic cells and monocytes/macrophages can express multiple receptors to recognize pathogenic microorganisms or antigen-antibody complexes, and take up antigenic substances through pinocytosis, phagocytosis and receptor-mediated endocytosis. B cells take up antigen mainly by B cell receptors concentrate and internalize antigen or pinocytosis. DC will present the antigen to the initial T cells, promoting T cell activation, proliferation and differentiation. Monocytes/macrophages and B cells present antigens to T helper cells(Th), and T helper cells further activate macrophages and B cells, and improve cellular and humoral immunity. According to its cellular function, it can be divided into professional APC and non-professional APC. The former includes dendritic cells (DC), monocytes/macrophages, and B lymphocytes. They constitutively express MHC classⅡmolecules, costimulatory molecules and adhesion molecules, and have the function of directly ingesting, processing and presenting antigens. Non-professional APCs mainly include endothelial cells, epithelial cells and fibroblasts. In non-professional APCs, MHC class II molecules are generally not expressed or under-expressed, but can be induced by inflammation or certain cytokines, and their ability to process and present antigens is weak. For APCs, endogenous antigens are presented by MHC class I molecules, which degrade and process the endogenous antigen, and then present the antigen peptides to CD8+ T cells in the form of antigen peptide-MHCI type molecular complexes. The endogenous antigen is mainly derived from an intracellular parasitic pathogen or mutational protein.

The process of antigen processing and presentation

Depending on the nature and source of the antigen, APC processes and presents antigens through four pathways: the MHC classⅠmolecular pathway, the MHC classⅡmolecular pathway, the non-canonical antigen presentation pathway, and the CD1 molecular pathway of lipid antigens. The MHC classⅠmolecular pathway is an endogenous antigen presenting pathway. Endogenous antigens bind to transporter associated with antigen processing (TAP) after ubiquitinated endogenous antigens are degraded by the proteasome. TAP selectively transports 8-12 amino acid antigen peptides to the endoplasmic reticulum (ER). The antigen polypeptide binds to the antigen-binding peptide groove of the MHC classⅠmolecule assembled by the endoplasmic reticulum to form an antigen peptide-MHCⅠ-like molecular complex. The complex is then transported to the cell membrane via the Golgi apparatus for recognition by CD8+ T cells, thereby completing antigen presentation process; the MHC class II molecular pathway is an exogenous antigen presenting pathway. The exogenous antigen are recognized and taken up by APC, and then APC will form endosomes or phagocytose lysosomes. After the endosomes or phagocytose lysosomes fuse with MHC classⅡ compartment (MⅡC), the antigen is degraded into a polypeptide. MIIC is the nonamer of MHCⅡ/Ii, in which the Ii chain is degraded in MIIC, leaving classⅡ-associated invariant chain peptide(CLIP) in the antigenic peptide binding groove of MHC classⅡmolecules. Under the action of HLA-DM, the CLIP of the antigen peptide binding groove is replaced by the antigen peptide to form a stable antigen peptide-MHC classⅡmolecular complex, which is then transported to the surface of the APC membrane for recognition by CD4+ T cells, thereby completing the antigen presentation process. Cross-presentation means that APC can uptake and process exogenous antigens to CD8+ T cells via MHC classⅠmolecular pathways or present endogenous antigens to CD4+ T cells via MHC class Ⅱmolecular pathways. The CD1 molecular pathway for lipid antigens is a pathway that specifically targets lipid antigens, mainly through the CD1 molecule on the surface of APC.

References:

  1. Deretic V., Fratti R. A. Mycobacterium tuberculosis phagosome. Molecular microbiology.1999, 31(6), 1603-1609.
  2. William R. H., Francis R. C. Cross-presentation in viral immunity and self-tolerance. Nature Reviews Immunology. 2001, 1: 126–134.

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