Host alloantigen–Major Histocompatibility Complex (MHC) (Allo-MHC complex)

Host alloantigen–Major Histocompatibility Complex (MHC) complexes are the specific molecular targets recognized by the T-cell receptors (TCRs) of Type 1 Regulatory T (Tr1) cells, particularly in the context of allogeneic transplantation (Roncarolo et al., 2018, Nature Reviews Immunology). These complexes consist of host-derived peptides presented on the surface of host cells by MHC (or HLA in humans) molecules. When a Tr1 cell encounters its cognate host alloantigen–MHC complex, it is activated to produce high levels of the immunosuppressive cytokines Interleukin-10 (IL-10) and Transforming Growth Factor-beta (TGF-β) (Gagliani et al., 2013, Nature Medicine). This localized cytokine release suppresses the activity of nearby effector T cells and modulates antigen-presenting cells, thereby promoting peripheral immune tolerance (Bacchetta et al., 2014, Frontiers in Immunology). This interaction is a cornerstone of therapeutic strategies aimed at preventing Graft-versus-Host Disease (GvHD) while maintaining the beneficial Graft-versus-Leukemia (GvL) effect. Current clinical developments, such as the T-allo10 cell therapy, focus on using these complexes to select or engineer Tr1 cells for adoptive cell therapy to treat transplant-related complications and autoimmune disorders (Gregori et al., 2010, Blood).

Other names

Host-specific HLA-peptide complexAllogeneic MHC-peptide complexTr1-recognized alloantigenDonor-specific HLA-peptide complex

Antigen-specific immune suppression via IL-10 and TGF-beta secretion