major histocompatibility complex

The major histocompatibility complex (MHC), called HLA (human leukocyte antigen) in humans, is a set of highly polymorphic genes on chromosome 6 encoding cell-surface proteins essential for adaptive immunity. MHC class I molecules (HLA-A, -B, -C) are expressed on all nucleated cells and platelets; they present endogenously synthesized peptides (e.g., viral, tumor antigens) via the cytosolic/proteasome-TAP pathway to CD8+ cytotoxic T lymphocytes, enabling recognition and killing of infected or malignant cells. MHC class II molecules (HLA-DP, -DQ, -DR) are expressed only on professional antigen-presenting cells (dendritic cells, macrophages, B cells) and thymic epithelium; they present exogenously derived peptides processed via the endosomal/lysosomal pathway to CD4+ helper T cells, activating humoral and cell-mediated immune responses. Peptide loading involves invariant chain and HLA-DM for class II, and TAP transporters plus tapasin for class I. MHC genes are codominantly expressed and inherited as haplotypes, contributing to extreme population diversity that underlies transplant rejection (matching HLA reduces graft-vs-host disease and rejection risk) and explains individual variability in immune responses to pathogens and vaccines. Certain HLA alleles show strong associations with autoimmune and inflammatory diseases, high-yield for boards: HLA-B27 (ankylosing spondylitis, reactive arthritis, psoriatic arthritis, IBD-associated arthritis - PAIR), HLA-DR3/DR4 (type 1 diabetes mellitus), HLA-DR2 (multiple sclerosis, Goodpasture syndrome), HLA-DR4 (rheumatoid arthritis), HLA-DQ2/DQ8 (celiac disease), HLA-B8 (Graves disease), and HLA-DR3 (Sjögren syndrome, SLE). MHC also plays a role in central T cell tolerance via positive/negative selection in the thymus, where T cells are selected based on their ability to recognize self-MHC without excessive self-reactivity.