Psoriasis patients demonstrate HLA-Cw*06:02 allele dosage-dependent T cell proliferation when treated with hair follicle-derived keratin 17 protein

Abstract

It is broadly accepted that psoriasis is an immune-mediated disease with a heritable component, but it is not clear what causes inflammation in the skin. Previous research suggests that fragments of the keratin 17 (K17) protein, which are constitutively expressed in hair follicles, could act as autoantigens. In this study, we synthesized the K17 protein from mRNA derived from hair follicles and tested whether it elicited T cell responses depending on the patient genotype at the major susceptibility locus HLA-Cw*06:02. We treated peripheral blood-derived cells with the K17 protein and its short fragments to assess the T cell proliferation response using flow cytometry. Our analyses show a significantly stronger increase in cell proliferation among patients but not in healthy controls. We then examined whether the variation in T cell proliferation correlated with the patient HLA-Cw*06:02 risk genotype. Considering the affected status and patient genotype as two independent predictors, we fitted a linear model and showed that the HLA-Cw*06:02 allele dosage strongly predicted the T cell response. Our study findings suggest that the K17 protein likely acts as an autoantigen in psoriasis and that patients' risk genotype is strongly correlated with the magnitude of the response to this putative autoantigen.