Smith antigen in complex with HLA-DR15

The **Smith antigen in complex with HLA-DR15** refers to an *autoantigenic peptide* (specifically SmB/B’ 58-72, with the sequence LVLLRGENL) bound in the peptide-binding groove of the major histocompatibility complex (MHC) class II molecule HLA-DR15. This complex serves as an immunodominant target in systemic lupus erythematosus (SLE) and lupus nephritis (LN), where it is presented on antigen-presenting cells and recognized by autoreactive CD4+ T cells. Structural studies confirm that the SmB/B’ 58-72 peptide binds HLA-DR15 in a manner accessible to T cell receptors, playing a direct role in autoimmunity induction and maintenance[1][4][8]. Recent advances have enabled the redirection of regulatory T cells (Tregs) with TCRs specific for this complex, demonstrating promising suppression of autoimmune responses in vitro and in vivo models relevant to lupus nephritis, suggesting a foundational platform for cell-based immunotherapies[1][4][6]. The complex is implicated in SLE pathogenesis via the presentation of self-antigenic epitopes leading to a loss of self-tolerance and pathogenic T cell activation[1][4][6]. Detection of anti-Sm antibodies is clinically used as a biomarker for SLE activity and lupus nephritis risk[7]. Since the Smith antigen-HLA-DR15 complex's immunogenicity is highly restricted to individuals with HLA-DR15, therapeutic strategies based on this complex apply primarily to those carrying this haplotype[4][6].

Other names

SmB/B’ 58-72 in complex with HLA-DR15Smith epitope-HLA-DR15 complexSm-HLA-DR15

Antigen-specific regulatory T cell redirection (using TCRs targeting the Smith antigen-HLA-DR15 complex)[1][4][6]; Immune modulation via autoreactive Treg induction or enhancement