Antigen Processing and Presentation

Antigen Presentation

The antigen presented on MHCs is recognised by T cells using a T cell receptor (TCR). These are antigen-specific.

T Cell Receptors

Each T cell has thousands of TCRs, each with a unique specificity that collectively allows our immune system to recognise a wide array of antigens.

This diversity in TCRs is achieved through a process called V(D)J recombination during development in the thymus. TCR chains have a variable region where gene segments are randomly rearranged, using the proteins RAG1 and RAG2 to initiate cleavage and non-homologous end joining to rejoin the chains.

The diversity of the TCRs can be further increased by inserting or deleting nucleotides at the junctions of gene segments; together forming the potential to create up to 10¹⁵ unique TCRs.

TCRs are specific not only for a particular antigen but also for a specific MHC molecule. T cells will only recognise an antigen if a specific antigen with a specific MHC molecule is present: this phenomenon is called MHC restriction.

Co-Receptors

As well as the TCR, another T cell molecule is required for antigen recognition and is known as a co-receptor. These are either a CD4 or CD8 molecule:

• CD4 is present on T helper cells and only binds to antigen-MHC II complexes.
• CD8 is present on cytotoxic T cells and only binds to antigen-MHC I complexes.

This, therefore, leads to very different effects. Antigens presented with MHC II will activate T helper cells and antigens presented with MHC I activate cytotoxic T cells. Cytotoxic T cells will kill the cells that they recognise, whereas T helper cells have a broader range of effects on the presenting cell such as activation to produce antibodies (in the case of B cells) or activation of macrophages to kill their intracellular pathogens.

Antigen Processing

Before an antigen can be presented, it must first be processed. Processing transforms proteins into antigenic peptides.

MHC Class I Molecules

Intracellular peptides for MHC class I presentation are made by proteases and the proteasome in the cytosol, then transported into the endoplasmic reticulum via TAP (Transporter associated with Antigen Processing) to be further processed.

They are then assembled together with MHC I molecules and travel to the cell surface ready for presentation.

Scray / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)

Fig 1
Diagram demonstrating the production of peptides for MHC class I presentation

MCH Class II Molecules

The route of processing for exogenous antigens for MHC class II presentation begins with endocytosis of the antigen. Once inside the cell, they are encased within endosomes that acidify and activate proteases, to degrade the antigen.

MHC class II molecules are transported into endocytic vesicles where they bind peptide antigen and then travel to the cell surface.

OpenStax College / CC BY (https://creativecommons.org/licenses/by/3.0)

Fig 2
Diagram showing processing of antigens for MHC Class II presentation by a dendritic cell