T-Cell-Receptor Repertoire in Chronic Plaque-Stage Psoriasis Is Restricted and Lacks Enrichment of Superantigen-Associated Vβ Regions

Abstract

Preferential usage of certain T-cell receptors by the lymphocytic infiltrate in psoriasis might indicate the involvement of an antigen in the pathogenesis of this disease. However, to date there are no data on the complete T-cell-receptor V alpha and V beta repertoire in psoriatic patients. We therefore compared the usage of T-cell-receptor variable regions in blood and skin of 10 patients with chronic plaque-stage psoriasis by means of semiquantitative polymerase chain reaction. Additionally, HLA class II alleles were analyzed by means of sequence-specific oligonucleotide typing. A considerable restriction of the T-cell-receptor repertoire was observed in the skin, where up to 20% of the variable regions present in the blood were not detectable. This was true for both alpha- and beta-chains. However, no interindividually constant pattern of T-cell-receptor restriction was deducible. Inconsistently, a certain preferential usage of some beta chains occurred within the cutaneous compartment. This report on the complete T-cell-receptor V alpha and V beta repertoire in psoriasis documents the restricted receptor repertoire of infiltrating T cells and a lack of enrichment of superantigen-associated V beta regions. Thus superantigens seem not to play a pathogenetically relevant role in chronic plaque-stage psoriasis.

Immunopathogenesis of Psoriasis: News in an Old Concept

“…Here again the old knowledge of initiation and exacerbation of psoriasis following throat infection has taken profit from recent insights on bacterial superantigens which have the capacity to interact with specific T receptor variable beta (VB) chain. The demonstration – at least in some studies – of a selective expansion of T cells expressing certain VB elements in psoriatic lesions supports the possible involvement of superantigens in lymphocyte stimulation [22, 23], even if a role for classical (auto)antigens and autoreactive T cells is also compatible with recent experimental data [20, 24]. …”

Sural nerve T-cell receptor Vβ gene utilization in chronic inflammatory demyelinating polyneuropathy and vasculitic neuropathy

“…38 At least five reasons why antigendriven selection of certain TCR are difficult to unveil, can be given: 1) the majority of infiltrating T cells in nerve may not recognize antigen, thus masking the antigen-specific population; 2) larger sized antigens might comprise multiple epitopes that are recognized by different TCR, thus leading to the presence of a multiclonal T cell population; 3) even a given epitope might activate T cells characterized by different receptors depending on the antigen presenting molecule(s) 38,39 ; 4) at the time the biopsy was taken, antigen-specific T cells may already have disappeared; and 5) the major pathology in CIDP is within proximal portions of the peripheral nervous system, and the findings in the sural nerve at ankle level may not reflect the active process more proximally.…”

Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis

“…Because psoriatic patients are often colonized with Staphylococcus and Streptococcus (2), and scratching of the skin would be expected to mimic tape-stripping by both compromising the barrier function and activating the epidermis (23), this alternative mechanism may explain why some psoriatic patients report improvement of their disease activity after treatment with oral antibiotics (40). It may also account for several reports that fail to demonstrate selective expansion of TCR Vβs in the skin of patients with plaque psoriasis (41,42). In this regard, epicutaneous application of SAg's on psoriatic skin may result in an acute inflammatory, HK-mediated response rather than SAg-mediated T-cell activation.…”