Antigen Processing and Presentation

Introduction

Antigen processing and presentation is a fundamental immune mechanism that allows the immune system to recognize and respond to foreign antigens, such as those from pathogens or abnormal cells. This intricate process involves the breakdown of antigens, their presentation on major histocompatibility complex (MHC) molecules, and subsequent activation of immune cells.

Understanding antigen processing and presentation is crucial for medical professionals, especially those in immunology, infectious diseases, and oncology. This article provides a comprehensive overview of antigen processing and presentation, including its types, function, related studies, treatment considerations, and clinical significance.

• Antigens must be presented to the adaptive immune system so that
  • specialized antigen presenting cells (APCs) can activate the immune system
  • killer T-cells can monitor the intracellular contents of all cells
  • helper T-cells can be alerted to both intracellular and extracellular antigens
• Two types of antigens are processed by cells for presentation on the cell surface
  • endogenous antigens are proteins produced by the cell
  • exogenous antigens are proteins that are taken up by the cell
• Both types are linked to major histocompatability complexes (MHC) during processing so that
  • they can be stably exported to the cell surface
  • they can be recognized specifically by T-cells
• Antigens are presented to two distinct cell populations including
  • CD4+ helper T-cells that
    • recognize antigens loaded onto MHC class II
  • CD8+ killer T-cells that
• recognize antigens loaded onto MHC class I

Antigen Processing

• Antigens must undergo a number of transformations before being presented including
  • degradation of proteins into component peptides
  • translocation of the peptides into the appropriate compartment
  • loading of the peptides onto MHC proteins
• The processing of antigens must therefore preserve information about
  • the location from where the antigen originated
• the type of response that is required

Antigen Processing Pathways

Feature	MHC Class I	MHC Class II
Function	Allow for sampling of intracellular antigensSignal that a cell is infected or abnormal	Allow for sampling of extracellular antigensSignal that pathogens are within the host
Target cell	CD8+ killer T-cellsRule of 8: (MHC) 1 x (CD) 8 = 8	CD4+ helper T-cells Rule of 8: (MHC) 2 x (CD) 4 = 8
Antigens	Endogenous antigens	Exogenous antigens
Degradation	By proteosomes in the cytosol	By proteases in the phagosome
Translocation	Into ER by TAP proteins	Into endosomes after phagocytosis
Loading	Directly bind to MHC I	Bind to MHC II after release of invariant chain
Defect	Absent CD8+ activity	Absent CD4+ activity

Antigen Presentation

• After processing, antigenic peptides are loaded on surface MHC proteins where
  • T-cell receptors can bind specifically to the peptide
  • CD4 and CD8 can bind specifically to the corresponding MHC
  • Integrins can bind APCs
• Together, this set of interactions allows for
  • specific detection of antigens
• activation of T-cells 

Function of Antigen Processing and Presentation:

The primary role of antigen processing and presentation is to alert the immune system to the presence of foreign antigens, triggering immune responses:

1. Dendritic Cells (DCs): DCs are professional antigen-presenting cells (APCs) that capture, process, and present antigens to immune cells. They play a crucial role in initiating immune responses.
2. T Lymphocytes: Antigen presentation by APCs activates T lymphocytes (T cells), which are central players in adaptive immune responses.

Types of Antigen Processing and Presentation:

1. Endogenous Pathway (MHC Class I): Intracellular pathogens or abnormal cells are targeted by cytotoxic CD8+ T cells through MHC class I presentation. Infected or cancerous cells present antigens on MHC class I molecules for recognition by CD8+ T cells.
2. Exogenous Pathway (MHC Class II): Extracellular pathogens are processed by APCs and presented on MHC class II molecules. Helper CD4+ T cells recognize these antigens, orchestrating immune responses against the pathogens.

Clinical Significance:

1. Immune Responses: Antigen processing and presentation are essential for effective immune responses against infections, cancers, and autoimmune disorders.
2. Vaccine Development: Understanding this process is crucial for designing effective vaccines that elicit strong immune responses.

Antigen Processing and Presentation Studies:

1. Mechanistic Studies: Laboratory studies investigate the cellular and molecular mechanisms of antigen processing and presentation.
2. Vaccine Research: Researchers study the presentation of vaccine antigens to optimize vaccine design.

Treatment Considerations:

1. Cancer Immunotherapy: Understanding antigen presentation is crucial for developing cancer immunotherapies that enhance T cell responses against cancer cells.
2. Infectious Diseases: Targeting antigens for presentation can aid in the development of treatments against infections.

Future Directions:

1. Personalized Medicine: Research explores personalized approaches to harness antigen presentation for precision therapies.
2. Tumor Microenvironment: Investigating antigen presentation within the tumor microenvironment can enhance cancer immunotherapies.

Conclusion:

Antigen processing and presentation are vital processes that facilitate immune recognition and response against foreign antigens. These mechanisms involve the breakdown of antigens and their presentation on MHC molecules to immune cells. This process triggers immune responses against infections, cancers, and other abnormalities. Dendritic cells are key players in antigen presentation, initiating T cell responses.

Check out Interview Preparation, CV and Personal Statement Editing – The Finale.