What is the Major Histocompatibility Complex (MHC)?

From the Guidelines

The Major Histocompatibility Complex (MHC) is a cluster of genes on the short arm of chromosome 6 that play a crucial role in the immune system by encoding proteins that present antigenic peptides to T cells.

Key Components of MHC

• The MHC locus is broadly divided into three subclasses:
  • Class I region: includes genes such as HLA-A, HLA-B, and HLA-C, which encode proteins that present self- or cytosolic pathogens to CD8 T cells 1.
  • Class II region: includes genes such as HLA-DPA1, HLA-DPB1, HLA-DQA1, and HLA-DRB1, which encode proteins that present processed extracellular pathogens to CD4 T cells 1.
  • Class III region: contains additional genes implicated in immune and inflammatory responses, such as complement genes 1.

Function of MHC

• MHC class I and II genes encode proteins that form complexes that present antigenic peptides to T cells, influencing thymic selection and T-cell activation 1.
• The highly polymorphic nature of the human leukocyte antigen (HLA) genes within the MHC has contributed to the MHC region having the largest number of disease associations of any locus, genome-wide 1.

Importance of MHC in Disease

• Disease risk associated with the MHC is modulated by several underlying mechanisms, such as polymorphisms in the amino acid sequence of HLA-DRB1 changing the capability to present autoantigens or increasing the number of autoreactive T cells during thymic selection 1.
• Accurate HLA typing, especially for HLA-DR genes, is essential to ensure the safety and prognosis of organ transplantation 1.

From the Research

Definition and Function of MHC

• The Major Histocompatibility Complex (MHC) is a genomic region that contains genes encoding proteins involved in antigen presentation and plays a crucial role in the adaptive immune system 2.
• MHC molecules present endogenous and exogenous antigens to T lymphocytes for recognition and response, enabling the immune system to distinguish self from non-self 3.
• The MHC is essential for immune response to infectious diseases, immunosurveillance, and self/nonself recognition 4.

Structure and Organization of MHC

• The organization of MHC genes varies in different groups of vertebrates, but some characteristics, such as gene clusters and genetic polymorphisms, are maintained across all groups, indicating an evolutionary advantage 2.
• The MHC region is highly conserved during evolution, suggesting that its genes are important for survival 5.
• The human MHC region contains many duplicated, polymorphic genes associated with various diseases 6.

Importance of MHC in Immune Function

• MHC genes play a key role in protecting populations of vertebrate species from contagious cancer 4.
• Changes in the MHC profile of tumor cells allow effective evasion of the immune response 4.
• The study of MHC can provide insights into the genetics and immunology of tumors and organ transplants 4.