HLA-DR3 restricted environmental epitopes from the bacterium Clostridium tetani have T cell cross-reactivity to the SLE-related autoantigen SmD

• Published in: Frontiers in immunology Vol. 13; p. 928374
• Main Authors: Zhao, Zhenhuan, Anderson, Ashley N., Kannapell, Carol C., Kwok, William W., Gaskin, Felicia, Fu, Shu Man
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 31.10.2022
• Subjects: Autoantibodies; autoantigen; Autoantigens; Clostridium tetani; environmental bacteria; Epitopes, T-Lymphocyte; HLA-DR3; HLA-DR3 Antigen; Humans; Immunology; Lupus Erythematosus, Systemic; molecular mimicry; Smith D (SmD); T cell epitope; T-Lymphocytes; molecular mimicry; systemic lupus erythematosus (SLE); cross-reactive T cells; T cell epitope; environmental bacteria; Smith D (SmD); autoantigen; HLA-DR3
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.928374

HLA-DR3 (DR3) is one of the dominant HLA-DR alleles associated with systemic lupus erythematosus (SLE) susceptibility. Our previous studies showed multiple intramolecular DR3 restricted T cell epitopes in the Smith D (SmD) protein, from which we generated a non-homologous, bacterial epitope mimics library. From this library we identified ABC 247-261 Mimic as one new DR3 restricted bacterial T cell epitope from the ABC transporter ATP-binding protein in Clostridium tetani . It activated and induced autoreactive SmD 66-80 -specific T cells and induced autoantibodies to lupus-related autoantigens in vivo . Compared to healthy donors, SLE patients have a greater percentage of cross-reactive T cells to ABC 247-261 Mimic and SmD 66-80 . In addition, we analyzed the ability of single DR3 restricted Tetanus toxoid (TT) T cell epitopes to induce autoimmune T cells. We found that the immunodominant TT epitope TT 826-845 stimulated SmD 66-80 reactive T cells but failed to induce persistent anti-SmD autoantibodies compared to the ABC 247-261 Mimic. Thus, exposure to the ABC 247-261 Mimic epitope may contribute to autoimmunity in susceptible DR3 individuals.