Peptide-loaded major histocompatibility complex (MHC) class I and class II complexes (pMHC)

Peptide-loaded major histocompatibility complex (pMHC) class I and class II complexes are specialized molecular assemblies on the surface of antigen-presenting cells, particularly dendritic cells, that present processed peptide fragments to T cells [1]. MHC class I complexes present endogenous antigens to CD8+ cytotoxic T cells, while MHC class II complexes present exogenous antigens to CD4+ helper T cells, serving as the primary signal for adaptive immune recognition [2, 5]. This interaction is fundamental for the detection of intracellular pathogens and malignant transformations, as well as the maintenance of self-tolerance [1]. Dendritic cells are uniquely capable of cross-presentation, allowing them to load exogenous antigens onto MHC class I to prime naive CD8+ T cells [2]. In therapeutic contexts, these complexes are the focal point for cancer vaccines and TCR-based immunotherapies. Drugs like Tebentafusp and Afamitresgene autoleucel are engineered to specifically recognize particular peptide-HLA combinations on target cells, bypassing or enhancing natural immune recognition [3, 4]. The clinical utility of targeting pMHC complexes is often limited by the high polymorphism of the Human Leukocyte Antigen (HLA) system, requiring patient stratification based on specific HLA alleles [3]. Furthermore, immune evasion through the downregulation of MHC expression or the loss of specific HLA alleles remains a significant challenge in treating advanced malignancies [5].

Other names

HLA-peptide complexAntigen-MHC complexpMHC-IpMHC-IIMHC-peptide complexPeptide-MHC complex

T-cell receptor (TCR) binding and activation of CD8+ or CD4+ T cells