T-cell receptor recognizing collagen type II peptide presented by HLA-DRB1*04:01 or HLA-DRB1*01:01 (CII-specific TCR)

The T-cell receptor (TCR) recognizing the collagen type II (CII) peptide (residues 259-273) presented by HLA-DRB1*04:01 or HLA-DRB1*01:01 is a pivotal mediator of the autoimmune response in rheumatoid arthritis (RA) (Ge et al., 2022). This TCR specifically identifies an immunodominant epitope within CII, the primary structural protein of articular cartilage, with recognition often dependent on post-translational modifications such as galactosylation at lysine 264 (Ge et al., 2022). In individuals carrying the "shared epitope" HLA-DRB1 alleles, these autoreactive T cells escape central tolerance and drive chronic synovial inflammation and joint destruction through the secretion of pro-inflammatory cytokines like IL-17 and IFN-gamma (Caccamo et al., 2015). Because of its central role in disease pathogenesis, this TCR-peptide-MHC complex is a primary target for antigen-specific immunotherapies (ASIT) designed to restore immune homeostasis. Therapeutic strategies include tolerogenic vaccines, such as the liposomal formulation DEN-181, which aim to selectively induce anergy or expand regulatory T cells (Tregs) specific to the collagen epitope (Thomas et al., 2022). These approaches seek to suppress the pathogenic autoimmune response in the joints without compromising systemic immunity (Andersson et al., 2023).

Other names

Collagen II-specific T-cell receptorCII259-273-specific TCRGal264-CII-specific TCRHLA-DR4/DR1-restricted collagen II TCRCII-specific TCR

Induction of antigen-specific immune tolerance through the expansion of regulatory T cells (Tregs), induction of effector T-cell anergy or deletion, and bystander suppression of the autoimmune response in the joint synovium.