Human Leukocyte Antigen Class I Molecule

Human leukocyte antigen (HLA) class I molecules are cell surface glycoproteins encoded by genes within the major histocompatibility complex (MHC) on chromosome 6. They play a central role in the adaptive immune system by presenting peptide antigens derived from intracellular proteins to CD8+ cytotoxic T lymphocytes, enabling recognition and elimination of infected or malignant cells. HLA class I molecules are heterodimers composed of a polymorphic heavy (α) chain and a non-polymorphic light chain called β2-microglobulin. The α chain consists of three extracellular domains (α1, α2, and α3), a transmembrane region, and a short cytoplasmic tail. The α1 and α2 domains form the peptide-binding groove. Classical HLA class I molecules (HLA-A, -B, -C) are highly polymorphic, enabling presentation of a wide array of antigenic peptides. Nonclassical class I molecules (e.g., HLA-E, HLA-F, HLA-G) exhibit limited polymorphism and have specialized functions. HLA class I molecules are expressed on nearly all nucleated cells and present endogenous peptides to CD8+ T lymphocytes for immune surveillance and response initiation.