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Major Histocompatibility Complex (MHC) molecules, referred to as Human Leukocyte Antigen (HLA) in humans, are cell surface glycoproteins that play a pivotal role in the adaptive immune system (StatPearls, NBK546607). MHC Class I molecules are expressed on all nucleated cells and present endogenous peptides to CD8+ cytotoxic T cells, whereas MHC Class II molecules are primarily found on professional antigen-presenting cells (APCs) and present exogenous peptides to CD4+ helper T cells (Janeway's Immunobiology). Their fundamental biological function is the presentation of peptide antigens to T-cell receptors, enabling the discrimination between self and non-self (PubMed, 29930553). In clinical pathology, MHC molecules are implicated in autoimmune diseases, transplant rejection, and cancer, where tumor cells frequently downregulate MHC expression to evade immune surveillance (Nature Reviews Immunology, nri1603). Therapeutic interventions include glatiramoids like glatiramer acetate, which competitively bind MHC Class II molecules to treat multiple sclerosis (PubChem, CID 71306437), and modern immunotherapies such as TCR-engineered T cells and bispecific T-cell engagers that target specific MHC-peptide complexes (Frontiers in Immunology, 10.3389/fimmu.2020.01498).
Drugs targeting MHC molecules typically act by competing with endogenous peptides for the binding groove to modulate immune responses or by serving as a specific recognition element for engineered T-cell receptors (TCRs) and TCR-mimetic antibodies to facilitate targeted cell lysis.
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