Major histocompatibility complex class II presenting citrullinated alpha-enolase (ENO1) peptides (MHC II-citENO1)

Major histocompatibility complex (MHC) class II molecules presenting citrullinated alpha-enolase (ENO1) peptides are specialized antigen complexes that serve as critical neoantigen targets in oncology and drivers of pathology in autoimmunity. Citrullination is a post-translational modification where the enzyme peptidylarginine deiminase (PAD) converts arginine residues into citrulline, a process frequently induced by cellular stress, hypoxia, or inflammation within the tumor microenvironment (Brentville et al., 2016, Cancer Research). While MHC class II molecules are traditionally associated with professional antigen-presenting cells, many tumor cells can be induced to express them, allowing for the direct recognition of citrullinated neoantigens by CD4+ T cells. In the context of cancer immunotherapy, these complexes are targeted by vaccines such as Modi-1, which utilize citrullinated ENO1 peptides to stimulate a robust Th1-mediated anti-tumor response capable of overcoming the immunosuppressive nature of the tumor microenvironment (Cook et al., 2018, Frontiers in Immunology). Conversely, in rheumatoid arthritis, the presentation of citrullinated ENO1 peptides by specific HLA-DR alleles is a hallmark of the loss of self-tolerance, leading to the production of anti-citrullinated protein antibodies (ACPA) and chronic joint inflammation (Congia et al., 2010, Journal of Autoimmunity). Understanding the dual role of this target is essential for developing therapies that can selectively activate the immune system against tumors without triggering or worsening autoimmune conditions.

Other names

Citrullinated ENO1-MHC II complexcit-ENO1-HLA-DR complexCitrullinated alpha-enolase peptide-MHC complexMHC class II-citrullinated enolase neoantigen

Induction of a potent CD4+ T-cell mediated immune response (specifically Th1) against cells that present citrullinated alpha-enolase peptides on their surface MHC class II molecules.