TCR recognition of peptide-HLA class II complexes in autoimmunity: Structural insights for therapeutic targeting - PubMed
5 hours ago
- #Therapeutic targeting
- #Autoimmunity
- #HLA class II
- Autoimmune diseases involve self-reactive T and B cells breaking immune tolerance, leading to chronic inflammation.
- Current treatments like immunosuppressants and biologics often fail to achieve long-term drug-free remission.
- HLA class II genes, highly polymorphic, are major risk factors for autoimmune diseases.
- Polymorphisms in HLA class II affect the peptide-binding groove, influencing self-peptide presentation and autoreactive T-cell activation.
- Only 38 resolved human TCR-pHLA II complexes linked to autoimmunity exist, with 19 related to celiac disease.
- Structural insights are guiding new therapies like pHLA II-based nanomedicines, engineered Tregs, and TCR-like antibodies.
- AI and machine learning could enable personalized therapies by integrating HLA genotype, peptide presentation, and T-cell repertoire data.