Major histocompatibility complex molecules presenting Medicago sativa-derived peptides

Major histocompatibility complex (MHC) molecules presenting Medicago sativa-derived peptides represent a pathological immune complex central to the development of alfalfa-induced systemic lupus erythematosus (SLE). The primary driver of this process is L-canavanine, a non-proteinogenic amino acid found in high concentrations in alfalfa (Medicago sativa) seeds and sprouts. L-canavanine acts as a structural analog of L-arginine and can be mistakenly incorporated into host proteins during translation, leading to the production of aberrant, misfolded "canavanyl-proteins." These proteins are subsequently processed by the proteasome or endosomal proteases and presented on the cell surface by MHC Class I and Class II molecules. Because these peptides contain a non-canonical amino acid, they are recognized as neoantigens (neoepitopes) by the immune system, effectively bypassing central tolerance and triggering an autoimmune response. This response is characterized by the activation of autoreactive T cells and the production of autoantibodies, leading to a clinical syndrome that mimics or exacerbates SLE. Interacting substances include L-canavanine itself, which serves as the substrate for neoantigen formation, and L-arginine, which can competitively inhibit this process. Therapeutic management often involves drugs like hydroxychloroquine, which interferes with MHC-mediated antigen processing, and standard immunosuppressants to mitigate the resulting autoimmune cascade.

Other names

MHC-canavanyl peptide complexAlfalfa-induced neoantigen-MHC complexCanavanine-containing peptide-MHC complexMHC molecules presenting canavanine-containing peptides