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MHC Class I vs MHC Class II: Key Differences and Functions

Major Histocompatibility Complex (MHC) molecules are essential for immune recognition and response. They are specialized glycoproteins that present antigens to T cells, allowing the immune system to identify and eliminate pathogens or abnormal cells. MHC molecules are classified into Class I and Class II, each with distinct structures, functions, and roles in immune defense.


This article explores the differences between MHC class I and MHC class II, highlighting their unique features and immune significance.


1. Overview of MHC Molecules

MHC molecules play a crucial role in antigen presentation, enabling the adaptive immune system to recognize infected or abnormal cells.


  • MHC Class I: Found on almost all nucleated cells; presents antigens to CD8+ cytotoxic T cells.
  • MHC Class II: Found on antigen-presenting cells (APCs); presents antigens to CD4+ helper T cells.

2. Key Differences Between MHC Class I and MHC Class II

Feature
MHC Class I
MHC Class II
Expression
Present on all nucleated cells.
Restricted to professional APCs (e.g., dendritic cells, macrophages, B cells).
Antigen Source
Endogenous (intracellular antigens, e.g., viral proteins).
Exogenous (extracellular antigens, e.g., bacterial toxins).
Associated T Cells
CD4+ helper T cells.
Peptide Binding Groove
Closed ends, binds peptides 8–10 amino acids long.
Open ends, binds peptides 13–25 amino acids long.
Structure
Composed of a heavy α chain and β2-microglobulin.
Composed of α and β chains of equal size.
Peptide Loading Site
Endoplasmic reticulum (ER).
Specialized endosomal compartments.
Function
Kills infected or abnormal cells.
Activates immune responses and helps B cells produce antibodies.


3. Structure of MHC Class I and Class II

MHC Class I


  • Structure:
    • Consists of a heavy α chain (with α1, α2, and α3 domains) and a β2-microglobulin chain.
    • The α1 and α2 domains form the peptide-binding groove. 
    • The groove accommodates short peptides (8–10 amino acids) due to its closed ends.
  • Expression:
    • Found on the surface of all nucleated cells, ensuring cytotoxic T cells can recognize infected or malignant cells.

MHC Class II


  • Structure:
    • Composed of two chains: α chain and β chain, each with two domains (α1/β1 and α2/β2).
    • The α1 and β1 domains form the peptide-binding groove.
    • The groove binds longer peptides (13–25 amino acids) because it has open ends.

  • Expression:
    • Restricted to antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells.

4. Antigen Processing and Presentation

MHC Class I Pathway


Step
Details
Antigen Source
Endogenous antigens (e.g., viral proteins or tumor antigens).
Processing
Antigens are degraded by proteasomes into short peptides.
Peptide Loading
Peptides are transported into the ER by TAP (Transporter Associated with Antigen
Processing), where they bind to MHC class I molecules.
Presentation
Peptide-MHC complexes are transported to the cell surface to present to CD8+ cytotoxic T cells.


MHC Class II Pathway


Step
Details
Antigen Source
Exogenous antigens (e.g., bacterial toxins, extracellular pathogens).
Processing
Antigens are taken up via phagocytosis or endocytosis and degraded in acidic endosomes.
Peptide Loading
MHC class II molecules bind peptides in a specialized endosomal compartment after
the invariant chain is removed.
Presentation
Peptide-MHC complexes are transported to the cell surface to present to CD4+ helper T
cells.


5. Immune Functions

MHC Class I


  • Activates CD8+ cytotoxic T cells, which kill infected or malignant cells by inducing apoptosis.
  • Important for defending against intracellular pathogens, such as viruses.

MHC Class II


  • Activates CD4+ helper T cells, which coordinate the immune response.
    • Th1 cells: Enhance macrophage activity to kill intracellular bacteria.
    • Th2 cells: Help B cells produce antibodies against extracellular pathogens.
Essential for initiating adaptive immunity against extracellular pathogens.


6. Clinical Significance

Disease/Condition
Role of MHC Molecules
Autoimmune Diseases
Aberrant MHC presentation can trigger autoimmune responses (e.g., Type 1 diabetes, rheumatoid arthritis).
Transplant Rejection
MHC molecules are critical for tissue compatibility; mismatches trigger rejection.
Cancer
Downregulation of MHC class I by tumor cells allows them to evade immune surveillance.
Vaccines
Effective vaccines require antigens that can be presented by MHC class I or II molecules
to elicit strong immune responses.

7. Summary Table

Feature
MHC Class I
MHC Class II
Expression
All nucleated cells.
Antigen-presenting cells (APCs).
T Cell Interaction
CD4+ helper T cells.
Antigen Source
Endogenous (intracellular pathogens).
Exogenous (extracellular pathogens).
Peptide Length
8–10 amino acids.
13–25 amino acids.
Function
Cytotoxic T cell activation; cell killing.
Helper T cell activation; immune coordination.


Conclusion

MHC class I and class II molecules are indispensable components of the adaptive immune system, enabling the recognition and elimination of pathogens and abnormal cells. While MHC class I activates cytotoxic responses to intracellular threats, MHC class II orchestrates helper T cell-mediated responses to extracellular pathogens. Understanding these molecules is key to advancing immunotherapy, vaccine development, and transplant medicine.


References

  1. Alberts, B., et al., 2015. Molecular Biology of the Cell. 6th Edition. Garland Science.
  2. Janeway, C.A., et al., 2001. Immunobiology: The Immune System in Health and Disease. Garland Publishing.
  3. Neefjes, J., et al., 2011. MHC class I and II antigen presentation. Nature Reviews Immunology, 11(12), pp.823-836.
  4. Rock, K.L., et al., 2016. Pathways of antigen processing and presentation. Immunology Reviews, 272(1), pp.9-27.
  5. Klein, J., Sato, A., 2000. The HLA system: Genetics, immunology, clinical testing, and clinical implications. Blood, 95(8), pp.2607-2620.

22nd Nov 2024 Shanza Riaz

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