Major Histocompatibility Complex (MHC)

Major Histocompatibility Complex (MHC)

Definition: The Major Histocompatibility Complex (MHC) is a set of cell surface proteins essential for the adaptive immune system. MHC molecules present peptide fragments derived from pathogens (antigens) to T cells, playing a critical role in immune recognition and response.

Types of MHC Molecules

• MHC Class I:

• Structure: Composed of a heavy chain (α chain) and a β2-microglobulin. It presents antigens to CD8+ cytotoxic T cells.
• Function: Found on nearly all nucleated cells, MHC Class I molecules present endogenous antigens (e.g., viral proteins) to T cells, facilitating the destruction of infected or malignant cells.

• MHC Class II:

• Structure: Composed of two chains (α and β) that are both polymorphic. It presents antigens to CD4+ helper T cells.
• Function: Primarily expressed on professional antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells. MHC Class II molecules present exogenous antigens (e.g., from phagocytized pathogens) to help activate T cells.

Functions of MHC

• Antigen Presentation: MHC molecules bind peptide fragments and display them on the cell surface for recognition by T cell receptors (TCRs). This interaction is crucial for T cell activation.
• Self vs. Non-Self Discrimination: MHC molecules help the immune system distinguish between self and foreign antigens, preventing autoimmune responses while promoting the elimination of pathogens.
• Transplant Compatibility: MHC molecules are key determinants in organ transplantation; mismatched MHC can lead to graft rejection.

Clinical Relevance

• Transplantation: Matching donor and recipient MHC types is critical to minimize rejection risks in organ transplants.
• Autoimmune Diseases: Certain MHC alleles are associated with increased susceptibility to autoimmune diseases (e.g., HLA-B27 with ankylosing spondylitis).
• Infectious Diseases: Variations in MHC genes can influence an individual’s ability to respond to infections and vaccines.

Conclusion

The Major Histocompatibility Complex is fundamental to the immune system’s ability to recognize and respond to pathogens. Understanding its structure and function is essential for advancements in immunology, transplantation, and therapeutic interventions.

References

1. Janeway CA Jr., et al. “Immunobiology.” 5th ed. Garland Science; 2001.
2. Abbas AK, Lichtman AH, Pillai S. “Cellular and Molecular Immunology.” 9th ed. Elsevier; 2017.
3. Pamer EG, Cresswell P. “Mechanisms of MHC class I–restricted antigen processing and presentation.” Annual Review of Immunology. 1998; 16(1): 323-358. DOI: 10.1146/annurev.immunol.16.1.323