Antigen presentation

Antigen presentation is a vital immune process where antigen-presenting cells (APCs) process and present antigens on their surface to T cells. This process is crucial for the activation of T cells, which play a significant role in the body's immune response. Antigen presentation involves the display of antigen fragments bound to major histocompatibility complex (MHC) molecules on the surface of APCs. There are two main types of MHC molecules involved in antigen presentation: MHC class I and MHC class II, each serving distinct functions and presenting antigens to different types of T cells.

Overview

Antigen presentation is a complex process that begins when an APC, such as a dendritic cell, macrophage, or B cell, ingests a pathogen or pathogen-infected cell. The pathogen is broken down into smaller fragments, including antigens, inside the APC. These antigens are then loaded onto MHC molecules. MHC class I molecules present antigens to CD8+ T cells (cytotoxic T cells), while MHC class II molecules present antigens to CD4+ T cells (helper T cells).

MHC Class I Antigen Presentation

MHC class I molecules are found on almost all nucleated cells and are responsible for presenting endogenous antigens (those originating from within the cell) to CD8+ T cells. This pathway is crucial for identifying and eliminating cells infected by viruses or transformed by cancer. When a cell becomes infected, viral proteins are synthesized in the cytoplasm and degraded into peptides by the proteasome. These peptides are then transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP), where they bind to MHC class I molecules. The MHC class I-peptide complex is then transported to the cell surface for recognition by CD8+ T cells.

MHC Class II Antigen Presentation

MHC class II molecules are primarily expressed on professional APCs and are involved in presenting exogenous antigens (those originating from outside the cell) to CD4+ T cells. This pathway is essential for initiating immune responses against pathogens that do not infect cells directly, such as bacteria in the extracellular space. In this pathway, APCs ingest pathogens through phagocytosis or endocytosis, and the ingested material is degraded in lysosomes. The resulting antigenic peptides are loaded onto MHC class II molecules in a specialized compartment called the MHC class II loading compartment. The MHC class II-peptide complex is then transported to the cell surface for recognition by CD4+ T cells.

Role in Immune Response

Antigen presentation is critical for the activation of T cells, which are central to the adaptive immune response. Once a T cell recognizes an antigen-MHC complex, it becomes activated and can proliferate and differentiate into effector cells. CD8+ T cells can directly kill infected or cancerous cells, while CD4+ T cells help orchestrate the immune response by producing cytokines that activate other immune cells, including B cells, which produce antibodies against the pathogen.

Clinical Significance

Understanding antigen presentation has significant implications for vaccine development, cancer immunotherapy, and the treatment of autoimmune diseases. By manipulating the antigen presentation process, scientists can design vaccines that elicit strong protective immune responses or develop therapies that enhance the immune system's ability to target and destroy cancer cells. Conversely, in autoimmune diseases, where the immune system mistakenly attacks the body's own cells, therapies that modulate antigen presentation can help reduce inappropriate immune responses.