ANTIGENIC PEPTIDES FOR THE DIAGNOSIS, THERAPY-MONITORING AND TREATMENT OF PSORIASIS

ANTIGENIC PEPTIDES FOR THE DIAGNOSIS, THERAPY-MONITORING AND TREATMENT OF PSORIASIS

CHALLENGE

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.

INNOVATION

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.

Figure: TCR hybridoma activation a) in direct contact with primary human melanocytes; b) by primary human melanocytes in dependence of HLA-Cw*0602

COMMERCIAL OPPORTUNITIES

  • 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

DEVELOPMENT STATUS

Proof of concept.

REFERENCES:

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.

Dr. Stephan Hohmann
E-Mail:
Reference Number:
Phone:
shohmann@baypat.de
B75034
+49 (0) 89 5480177 - 36