MHC I and MHC II: Summary of Antigen Processing and Presentation

The pathways for obtaining antigenic peptides to load into Major Histocompatibility Complex (MHC) Class I and Class II molecules differ due to the distinct roles and mechanisms of these two classes of MHC molecules in the immune system.

MHC Class I Pathway

Antigenic peptides presented by MHC Class I molecules are derived mainly from endogenous proteins synthesized within the cell. The pathway for loading antigenic peptides onto MHC Class I molecules is termed the endogenous pathway or cytosolic pathway. It involves the following steps:

Protein Degradation in the Cytosol: Endogenous proteins within the cell are degraded into short peptide fragments by the proteasome, a large protein complex.

Transport into the Endoplasmic Reticulum (ER): The resulting peptide fragments, typically 8-10 amino acids in length, are transported into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP) complex.

Peptide Loading onto MHC Class I Molecules: Inside the ER, these peptides are loaded onto nascent MHC Class I molecules that are being synthesized. This occurs in a process facilitated by chaperone proteins such as tapasin.

Transport to the Cell Surface: Loaded MHC Class I molecules are then transported from the ER through the Golgi apparatus to the cell surface, where they present the antigenic peptides to CD8+ T cells, which play a role in cytotoxic T lymphocyte (CTL) responses.

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MHC Class II Pathway

Antigenic peptides presented by MHC Class II molecules are derived from exogenous proteins that are taken up by antigen-presenting cells (APCs) from the extracellular environment. The pathway for loading antigenic peptides onto MHC Class II molecules is termed the exogenous pathway and involves the following steps:

Antigen Uptake: APCs such as dendritic cells, macrophages, and B cells phagocytose or endocytose extracellular material containing antigenic proteins.

Protein Degradation in Endosomes or Phagosomes: The engulfed antigens are degraded into peptide fragments within endosomes or phagosomes by proteases.

MHC Class II Synthesis and Peptide Loading in Endosomes/Phagosomes: MHC Class II molecules are synthesized in the endoplasmic reticulum and then transported to endosomes or phagosomes. Within these compartments, MHC Class II molecules bind to a chaperone protein called the invariant chain (Ii), which prevents premature peptide binding. As the antigen is degraded, a fragment of Ii called CLIP remains bound to the MHC Class II molecule. CLIP is subsequently exchanged for the antigenic peptide by the action of HLA-DM (in humans) or H2-M (in mice).

Transport to the Cell Surface: The MHC Class II molecule, now loaded with the antigenic peptide, is transported to the cell surface where it presents the peptide to CD4+ T cells, which are involved in helper T cell responses.

These pathways ensure that both endogenous and exogenous antigens are efficiently presented to T cells, allowing for the activation of appropriate immune responses.

Next Topic: Presenting Endogenous and Exogenous Antigens

Source: ChatGPT response prompted and edited by Joel Graff.

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