Major histocompatibility complex class I and class II (MHC class I and MHC class II)

Major histocompatibility complex class I and class II proteins are cell-surface receptors that play central roles in the adaptive immune system by presenting peptides to T cells for immune surveillance[3][4][6]. MHC class I molecules are composed of a heavy α chain (with α1, α2, and α3 domains) associated with β2-microglobulin, and are expressed on nearly all nucleated cells to present endogenous antigens (typically from viruses or cancers) to CD8+ cytotoxic T lymphocytes[5][7][1]. MHC class II molecules are heterodimers of α and β chains (each with two extracellular domains), restricted to professional antigen-presenting cells (such as dendritic cells, macrophages, and B cells), and present exogenous antigens to CD4+ helper T cells[1][2][5][6]. Both classes are highly polymorphic, with extensive allelic variants (notably HLA in humans), underpinning their critical roles in disease susceptibility, transplant success, and autoimmunity. Drugs and therapeutic interventions may affect or exploit MHC-mediated antigen presentation directly or indirectly, for example, checkpoint inhibitors rely on functional MHC expression in tumors[3][7]. Safety concerns include the risk of triggering unwanted immune responses, such as autoimmunity or rejection of transplanted tissues[7].

Other names

MHC-I and MHC-IIHuman leukocyte antigen class I and II (HLA class I and HLA class II, in humans)Major histocompatibility antigen class I and II

Modulation of antigen presentation to T cells Blocking peptide binding/groove occupancy Altering T-cell recognition and activation Immune evasion or enhancement