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

The Major Histocompatibility Complex (MHC) Class I and II are essential components of the adaptive immune system, responsible for presenting peptide antigens to T cells. MHC Class I molecules are expressed on nearly all nucleated cells and present intracellularly derived peptides to CD8+ cytotoxic T cells, facilitating the detection of viral infections and malignant transformations [1, 5, 9]. MHC Class II molecules are primarily found on professional antigen-presenting cells, such as dendritic cells and macrophages, and present extracellularly derived peptides to CD4+ helper T cells to coordinate broader immune responses [2, 11, 16]. These molecules are highly polymorphic, which allows for a diverse range of antigen presentation across the human population but also serves as the primary barrier to successful organ transplantation [1, 10, 14]. In oncology, tumor cells often downregulate MHC expression to evade immune surveillance, making the restoration of MHC levels through agents like interferon-gamma or epigenetic modifiers a key therapeutic strategy [12, 15, 18]. Conversely, specific MHC alleles are strongly associated with susceptibility to various autoimmune diseases, where the complex inappropriately presents self-antigens to the immune system [3, 6, 20].

Other names

Human leukocyte antigen (HLA)MHC moleculesHistocompatibility antigensHLA class I and IITissue antigens

MHC molecules facilitate the presentation of peptide antigens to T-cell receptors (TCRs). MHC Class I molecules present endogenous peptides to CD8+ cytotoxic T cells, while MHC Class II molecules present exogenous peptides to CD4+ helper T cells. Therapeutic strategies include upregulating MHC expression to enhance anti-tumor immunity or modulating MHC-TCR interactions to treat autoimmune diseases and prevent transplant rejection.