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

Major Histocompatibility Complex (MHC) class I and II molecules, also known as Human Leukocyte Antigens (HLA) in humans, are essential cell-surface glycoproteins that mediate the adaptive immune response by presenting peptide antigens to T cells (Janeway et al., 2001). MHC class I molecules are expressed on nearly all nucleated cells and present endogenous peptides to CD8+ cytotoxic T cells, whereas MHC class II molecules are primarily expressed on professional antigen-presenting cells and present exogenous peptides to CD4+ helper T cells (NCBI, 2023). These molecules are critical for the immune system's ability to distinguish between self and non-self, facilitating the detection of pathogens and malignant cells. In drug development, MHC alleles are the structural basis for TCR-engineered T-cell therapies and neoantigen vaccines, which target specific peptide-MHC complexes (Nature Reviews Drug Discovery, 2020). However, the high degree of polymorphism within MHC genes poses a significant challenge, as it necessitates precise HLA matching for transplantation and limits the broad applicability of many immunotherapies to specific patient genotypes (StatPearls, 2023).

Other names

HLAHuman leukocyte antigenMHCMajor histocompatibility complex

MHC molecules present antigenic peptides to T-cell receptors (TCRs) to initiate immune responses. Therapeutic mechanisms include the use of engineered TCRs to target specific MHC-peptide complexes on tumor cells, the modulation of T-cell costimulation (e.g., via CTLA-4-Ig), and the inhibition of downstream T-cell signaling pathways (e.g., calcineurin inhibition) to prevent rejection or autoimmunity (Nature Reviews Drug Discovery, 2020; PubMed, 2022).