Selection of conserved TCR VDJ rearrangements in chronic psoriatic plaques indicates a common antigen in psoriasis vulgaris

Abstract

Psoriasis vulgaris is a common HLA-associated inflammatory skin disease. Although its etiology is still unknown, it is thought to involve T cell-mediated inflammatory mechanisms. In examining the lesional psoriatic TCR beta chain (TCRB) usage in a pair of identical twins concordant for psoriasis, we observed repetitive TCR VDJ rearrangements which indicated antigen-specific oligoclonal T cell expansion. Several of these TCRB rearrangements were identical or highly homologous in the amino acid composition of the complementarity determining region 3 (CDR3), suggesting that T cells with these TCR might be important for disease manifestation. This conclusion was strengthened by TCR analysis of other psoriasis patients. Several repetitive lesional TCRB rearrangements were found that were similar to the conserved CDR3 seen in the twins. Since TCR antigen specificity is largely determined by the beta chain CDR3, selection of T cells with conserved TCRB CDR3 motifs could indicate the presence of a common antigen as a major target of the lesional psoriatic immune response.

Predominance of activated, clonally expanded T helper type 17 cells within the CD4+ T cell population in psoriatic lesions

“…Evidence from the current study points to the expansion of Th17 cells in psoriatic lesions being driven by antigen. Analysis of TCR Vb chain usage revealed a skew towards limited clonality in lesional skin compared to peripheral blood, supporting and extending earlier observations of psoriatic skin T cells [38]. Recent sequencing of a panel of T cells cloned from psoriatic plaques indicated extensive sharing of TCR [39], and we confirm that similar overrepresentation can be found in unselected lesional cells isolated ex vivo.…”

“…© 2013 British Society for Immunology, Clinical and Experimental Immunology, 173:[38][39][40][41][42][43][44][45][46] …”

Psoriasis: the future

“…What is triggering the inflammatory response in psoriasis? Recent studies suggest that CD8 + T cells within the epidermis of psoriatic plaques exhibit Vβ restriction, 34 –36 implying that they are behaving in an antigen‐specific manner 36 . Various antigens have been hypothesized as being key to the psoriatic process, however, definitive proof of an antigen or autoantigen is elusive.…”

“…T cells found within psoriasis plaques can exhibit clonal specificity 34 –36 and vaccination against specific isotypes of the Vβ component of the T‐cell receptor, for instance, could induce anti‐psoriatic regulatory T‐cell activity, thereby deleting the disease causative T cells. This approach would most probably have to be administered on an individual basis as Vβ receptor T‐cell clones seem to show high interindividual variability 35 . This form of vaccination, too, may result in a switch from a Th1 to Th2 cytokine profile, a beneficial effect in psoriasis treatment 40 …”

Psoriasis after cord blood stem cell transplantation

“…It has been found that CD4 and CD8 T lymphocytes display a restricted repertoire in psoriasis, suggesting an antigenic stimulation of these T cells. These antigens are not known yet 9 . Recent data have shown that a keratinocyte alteration involving jun proteins as well as plasmacytoid predendritic cell activation is essential in initiating psoriasis lesions 10,11 .…”