MHC-Mediated Antigen Presentation

MHC-Mediated Antigen Presentation

• The immune system relies on recognizing and responding to foreign pathogens.
• The Major Histocompatibility Complex (MHC) is a key player in this process, presenting antigens to T cells.

Structure and Function of MHC Molecules

• MHC Class I: Found on all nucleated cells; presents endogenous (intracellular) antigens to CD8+ cytotoxic T cells.
  • Structure: Single α-chain with three domains (α1, α2, α3) and a β2-microglobulin.
  • Function: Presents antigens from intracellular pathogens (e.g., viruses).
• MHC Class II: Expressed primarily on antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells; presents exogenous (extracellular) antigens to CD4+ helper T cells.
  • Structure: Two chains (α and β) with two domains each (α1, α2, β1, β2).
  • Function: Presents antigens from sources outside the cell (e.g., bacteria, fungi, parasites).

General MHC Organization and Inheritance

• Gene Organization: MHC genes are located in a linked cluster on chromosome 6 (HLA complex).
• Inheritance: MHC genes are inherited codominantly (both maternal and paternal alleles expressed). They demonstrate linkage disequilibrium (certain allele combinations inherited together more often).
• Polymorphism: MHC has many different alleles, creating diverse antigen presentation capabilities vital for broad pathogen recognition. This is crucial for population survival.

MHC and Expression Patterns

• MHC Class I Expression: Found on all nucleated cells, allowing CD8+ T cells to monitor all cells for intracellular infections.
• MHC Class II Expression: Expressed on APCs (dendritic cells, macrophages, B cells). Cytokines like IFN-γ can upregulate MHC Class II expression during infection/inflammation.
• Role of MHC in Immune Responses: MHC molecules present antigens to T cells. T cell receptors (TCRs) recognize specific peptide-MHC complexes, distinguishing self from non-self. Expression can vary based on environmental factors, impacting pathogen detection.

Endogenous Antigen Processing and Presentation Pathway

• Proteasomes: Within infected/damaged cells, proteins are degraded into peptides.
• Transport into ER: Peptides enter the endoplasmic reticulum (ER) via TAP, the transporter associated with antigen-processing.
• MHC Class I Loading: Peptides bind to MHC class I molecules within the ER.
• Recognition by CD8+ T Cells: Cytotoxic T cells recognize peptide-MHC class I complexes and kill infected cells.

Exogenous Antigen Processing and Presentation Pathway

• Antigen Uptake: Antigen-presenting cells (APCs) take up extracellular antigens (e.g., bacteria) via phagocytosis/endocytosis.
• Processing in Endosomes: Antigens are degraded into peptides within endosomal vesicles.
• MHC Class II Loading: Peptides bind to MHC class II molecules within late endosomes/lysosomes.
• Transport to the Cell Surface: MHC class II-peptide complexes are transported to the cell surface for recognition by CD4+ helper T cells.

Cross-Presentation of Exogenous Antigens

• Cross-Presentation: Certain APCs (e.g., dendritic cells) can present exogenous antigens on MHC class I molecules.
• Significance: Crucial for activating CD8+ T cells against pathogens that don't infect APCs directly (e.g., viruses).

Presentation of Nonpeptide Antigens

• MHC-like Molecules (CD1 Family): Presents nonpeptide antigens (glycolipids, phospholipids) to T cells.
• Role in Immune Response: CD1 molecules present lipid antigens from bacteria (e.g., mycobacteria) to NKT cells, supporting immune responses against pathogens like tuberculosis.

Dive into the critical role of the Major Histocompatibility Complex (MHC) in the immune response. This quiz covers the structure and function of MHC Class I and Class II molecules, their interaction with T cells, and their organization and inheritance. Test your knowledge on how these mechanisms are essential for pathogen recognition.