Disease-specific autoantigen–Major Histocompatibility Complex (pMHC) (pMHC complex)

Disease-specific autoantigen–Major Histocompatibility Complex (pMHC) complexes are molecular assemblies consisting of a self-derived peptide (autoantigen) bound within the groove of an MHC (or HLA in humans) molecule. These complexes are presented on the surface of antigen-presenting cells or target tissues, where they are recognized by the T-cell receptors (TCRs) of autoreactive T-lymphocytes (1). In healthy individuals, central and peripheral tolerance mechanisms eliminate or suppress T-cells that recognize these self-complexes; however, in autoimmune diseases, this tolerance is broken, leading to the activation of pathogenic T-cells that attack the body's own tissues (2). Targeting these specific pMHC complexes is a cornerstone of antigen-specific immunotherapy, which aims to selectively modulate the immune response against the disease-causing antigen without inducing broad immunosuppression (3). Strategies include using soluble pMHC complexes or pMHC-coated nanoparticles (Navacims) to induce T-cell exhaustion or regulatory T-cell (Treg) differentiation, as well as developing T-cell receptor-like (TCRL) antibodies that specifically recognize the pMHC complex to block pathogenic interactions (4, 5).

Other names

Peptide-MHC complexpMHCAutoantigen-HLA complexSelf-peptide-MHC complexMHC-peptide complex

Induction of antigen-specific immune tolerance, deletion of autoreactive T-cells, or induction of regulatory T-cells (Tregs) by mimicking or blocking the interaction between the pMHC complex and the T-cell receptor (TCR).