MHC

The major histocompatibility complex (MHC) is a cluster of genes in vertebrates that encode cell-surface proteins essential for the adaptive immune system to recognize and respond to peptide antigens. In humans, the MHC region is located on chromosome 6 and is commonly referred to as the human leukocyte antigen (HLA) system. It comprises three main components: classical MHC class I genes, classical MHC class II genes, and the MHC class III region, which contains a variety of other immune-related genes. Non-classical MHC class I molecules, such as HLA-E, HLA-F, and HLA-G, also contribute to immune regulation.

Class I MHC molecules, including HLA-A, -B, and -C, present endogenous peptides to CD8+ T cells and are expressed on nearly all nucleated cells. Class II molecules, including HLA-DR, -DP, and -DQ, present exogenous peptides to CD4+ T helper cells and are mainly expressed on professional antigen-presenting cells such as dendritic cells, macrophages, and B cells. Antigen processing for class I involves proteasomal degradation of cytosolic proteins and peptide transport into the endoplasmic reticulum by TAP; class II peptides are generated in endosomal/lysosomal compartments with the aid of the invariant chain and CLIP.

The HLA genes are highly polymorphic and are expressed in a co-dominant manner, making individuals heterozygous for many alleles with diverse antigen-presenting capabilities. This diversity influences transplantation compatibility and susceptibility to autoimmune diseases. Notable associations include HLA-B27 with ankylosing spondylitis, HLA-DQ2/DQ8 with celiac disease, and HLA-B*57:01 with abacavir hypersensitivity; HLA-B*15:02 has been linked to carbamazepine-induced Stevens-Johnson syndrome in certain populations.

Evolutionarily, the extensive polymorphism of MHC genes is maintained by balancing selection, ensuring broad immune recognition across diverse pathogens.