ANTIGENIC PEPTIDES FOR THE DIAGNOSIS, THERAPY-MONITORING AND TREATMENT OF PSORIASIS
Psoriasis vulgaris is a frequent immune-mediated HLA-associated inflammatory skin disease affecting 120 to 180 million people worldwide. Many psoriasis features are consistent with a T-cell mediated autoimmune pathogenesis. Like other autoimmune diseases, psoriasis is linked to a particular HLA (human leukocyte antigens) class I allele (HLA-C*06:02).
Biochemical interactions between peptide epitopes, specific membrane molecules encoded by HLA and T-cell antigen receptors (TCR) are required to elict specific immune responses. The peptides are presented to the T-cells by HLA-molecules. T-cells express a clonotypic TCR on the surface and this receptor enables the T-cell to recognize peptide antigens bound to HLA molecules. In general, TCR recognition of HLA-peptide complexes results in T-cell activation, clonal expansion and differentatiation of T-cells into effector, memory and regulatory T-cells.
This technology was invented with the METHOD FOR IDENTIFICATION OF TARGET ANTIGENS OF T-CELLS and is based on the discovery that HLA-C*06 directs an autoimmune response against melanocytes and presents autoantigens to pathogenic T-cells in psoriasis. Using a recombinant TCR from a pathogenic lesional psoriatic T-cell clone of a HLA-Cw*06-positive psoriasis patient, it identifies epitopes form autoantigenic proteins in psoriasis. It shows that patients have circulating T-cells in peripheral blood, which specifically react against complexes composed of these peptides and HLA-Cw*06, and that complexes of said peptides and HLA-Cw*06 can be used to identify these peptide-specific T-cells. The technology also shows that blocking the interaction between HLA-Cw*06 and a pathogenic T-cell antigen receptor can inhibit T-cell activation. Blocking the interaction between HLA-C molecules and TCR is therefore considered as a treatment modality in psoriasis.
- Diagnosis of psoriasis
- Monitoring disease acitivity and efficacy of treatment
- Defining disease risk
- Treatment of psoriasis
- Using altered peptide ligands for creating immunotolerance against the autoantigens
- Providing a cure by eliminating the pathogenic CD8+ T cells using toxin-coupled
- Multimeric peptide/HLA-C*06:02 complexes
- Downregulating the pathogenic immune response by blocking HLA-C / T cell-interactions
Proof of concept.
Arakawa A, Siewert K, Stöhr J, et al. Melanocyte antigen triggers autoimmunity in human psoriasis. The Journal of Experimental Medicine. 2015;212(13):2203-2212. doi:10.1084/jem.20151093.