Major histocompatibility complex–peptide–T cell receptor axis (MHC–peptide–TCR axis)

The **major histocompatibility complex–peptide–T cell receptor axis** refers to the multi-molecular interface by which T cells recognize antigens presented by other cells. Endogenous or foreign peptides are loaded on major histocompatibility complex (MHC) molecules—called human leukocyte antigen (HLA) in humans—which present these peptides at the cell surface. The T cell receptor (TCR) of a T lymphocyte binds specifically to the peptide–MHC (pMHC) complex, determining the immune response specificity[1][2][3][5][7]. MHC class I molecules present shorter peptides (typically 8–10 amino acids, mostly to CD8+ T cells); class II molecules bind longer peptides and present them to CD4+ T cells[1][2]. The TCR–pMHC interaction is highly diverse yet governed by conserved structural features: the TCR binds diagonally atop the MHC, wherein TCR CDR1/2 loops interact mainly with MHC, while CDR3 loops contact the peptide[7]. This axis is essential for T cell activation, thymic selection, and adaptive immunity, but is also implicated in autoimmune diseases, cancer immunosurveillance, and infection. Therapeutic strategies target this axis via adoptive T cell therapies, TCR-mimic antibodies, and peptide vaccines, but these face challenges including off-target effects and immune escape[1][3][7].

Other names

MHC–peptide–TCR complexpMHC–TCRpeptide–MHC–TCR interfaceTCR–pMHC interaction

Enhancement or inhibition of TCR–pMHC interaction Redirection of T cell specificity via engineered TCRs Targeted lysis of cells presenting specific pMHC complexes Immune modulation by altering peptide presentation