Citrullinated peptide–Major Histocompatibility Complex class II complex (Cit-peptide–MHC II)

The Citrullinated peptide–Major Histocompatibility Complex (MHC) class II complex is a central molecular driver in the pathogenesis of rheumatoid arthritis (RA). It forms when self-proteins undergo citrullination—a post-translational modification where arginine is converted to citrulline by peptidylarginine deiminase (PAD) enzymes—and are subsequently presented by specific HLA-DR alleles known as the shared epitope (Scally et al., 2013). This complex is specifically recognized by the T-cell receptors (TCRs) of autoreactive CD4+ T cells, triggering an inflammatory cascade and the production of anti-citrullinated protein antibodies (ACPAs) (Malmström et al., 2017). Because this interaction is highly specific to the autoimmune response in RA, it is a primary target for next-generation antigen-specific immunotherapies. Current therapeutic strategies include tolerogenic vaccines, such as DEN-181, which are designed to induce immune tolerance to these complexes and restore homeostasis (Thomas et al., 2015). By targeting the Cit-peptide–MHC II complex, researchers aim to provide a precise treatment that avoids the broad immunosuppression associated with conventional RA therapies.

Other names

Citrullinated antigen–MHC II complexCit-peptide–HLA-DR complexCCP–MHC II complexCitrullinated peptide–HLA-DRB1 complex

Induction of antigen-specific immune tolerance, Regulatory T cell (Treg) induction, T cell receptor (TCR) antagonism, Deletion of autoreactive T cells