Major histocompatibility complex (MHC) (MHC)

The Major Histocompatibility Complex (MHC), referred to as the Human Leukocyte Antigen (HLA) system in humans, is a group of cell-surface glycoproteins essential for the adaptive immune system to distinguish self from non-self [1, 2]. MHC Class I molecules are expressed on nearly all nucleated cells and present endogenous peptides to CD8+ cytotoxic T cells, facilitating the detection and elimination of virally infected or malignant cells [2, 16]. MHC Class II molecules are primarily found on professional antigen-presenting cells, such as dendritic cells and macrophages, and present exogenous peptides to CD4+ helper T cells to coordinate broader immune responses [1, 12]. These molecules are highly polymorphic, and specific HLA alleles are strongly associated with susceptibility to various autoimmune diseases and severe drug hypersensitivity reactions, such as Stevens-Johnson Syndrome [14, 15]. In oncology, tumors often downregulate MHC expression to evade immune surveillance, while in transplantation, MHC mismatching is the primary driver of graft rejection and graft-versus-host disease [4, 15]. Therapeutic interventions include peptides like glatiramer acetate that compete for MHC binding, small molecules like abacavir that alter the peptide-binding pocket, and novel biologics like eftilagimod alpha that target MHC-receptor interactions [9, 11, 15]. Understanding MHC function is also critical for vaccine development, as effective vaccines must ensure that antigens are appropriately processed and presented to elicit a robust T-cell response [7, 16].

Other names

Human leukocyte antigenHLAMHC-IMHC-IITransplantation antigensHistocompatibility antigens

Competitive binding to the peptide-binding groove, alteration of the peptide-binding repertoire, and modulation of MHC-T-cell receptor interactions.