An 8-amino acid peptide encoding a sequence of the transmembrane region of the T cell receptor ␣ chain (TCR-␣) was shown to inhibit T cell function by preventing functional assembly of the T cell receptor (mimic peptide). To avoid systemic immunosuppression by peptide application in vivo, we used a topical application of the peptide. In the system of murine contact sensitivity, topical application of the peptide inhibited the elicitation of contact sensitivity following application of a contact allergen in sensitized animals. Alternatively, when naked DNA encoding the peptide sequence was injected into skin before application of a contact allergen to Keywords: TCR; T cell function; allergical contact dermatitis; T cell mediated disease; DNA vaccinationThe ␣, ␤ T cell receptor (TCR) is a multisubunit transmembrane complex composed of at least six different polypeptides (␣, ␤, ␥, ␦, ⑀ and ). 1 The TCR-␣ and -␤ subunits appear as a disulfide-linked homodimer that is the ligand binding site and determines the specificity of the receptor. For signal transduction into the cytoplasm, the TCR is noncovalently associated with the CD3 molecules (CD3-␥, -␦, -⑀ and -). The transmembrane region of the TCR is of critical importance for a functional assembly of the T cell receptor. 2 The transmembrane region of the TCR-␣ chain is highly conserved in different species. Studies on the assembly of the multisubunit TCR demonstrated that the stable interactions between the TCR-␣ chain and the CD3 molecule were located to eight amino acids within the transmembrane region of TCR-␣. [3][4][5] Manolios et al 6 demonstrated that an eight amino acid peptide mimicking the TCR-␣ chain inhibits T cell function in vitro and in vivo. These investigators showed the inhibitory effect of this peptide in different murine autoimmune disease models. The disadvantage of the systemic application of the mimic peptide is the general and long-lasting immunosuppressive effect that is unwanted for human applications.Allergic contact dermatitis (ACD) is an example for a T cell mediated delayed-type hypersensitivity (DTH) reaction. 7 ACD contains two main phases. During the sensitization phase epidermal Langerhans cells (LC) and

Background: Sublingual immunotherapy (SLIT) has been demonstrated to be a viable alternative to injection immunotherapy. Administration of high doses of allergens to ensure efficacy has been shown to be well tolerated. The aim of the present study was the first step to address the issue of fast-induction regimens using various induction SLIT regimens in paediatric and adult patients. Methods: Sixty-four patients (age range 5–46 years) with grass pollen rhinoconjunctivitis were enrolled in an 8-month double-blind, placebo-controlled trial of SLIT. Sixty-three patients were randomized to four groups and evaluated at the end of the study. One group received placebo (n = 16) and the other three groups (n = 47) received five grass pollen extracts according to three different induction regimens: regimen 1 starting with 3 IR tablets (n = 15), regimen 2 starting with 10 IR (n = 16) and regimen 3 starting with 30 IR (n = 16). The maintenance phase was made with sublingual-swallow drops at the same concentration of 300 IR/ml for all the patients. Adverse events were recorded on diary cards. Results: During induction phase, 25/47 patients in the SLIT groups had adverse reactions in comparison to 2/16 patients in the placebo group (p < 0.05). The rate of adverse reactions was 33.3% (11.8–61.6) (95% CI) for regimen 1, 31.3% (11.0–58.7) for regimen 2, 43.8% (19.8–70.1) for regimen 3 and 12.5% (1.6–38.3) for placebo. Fifty-seven reactions were local reactions involving the oral region (54 SLIT, 3 placebo) and 13 were systemic reactions (all in the SLIT groups). 11/13 reactions were mild (gastrointestinal disorders, rhinoconjunctivitis), 1/13 consisted of moderate asthma and 1/13 consisted of severe abdominal pain. No urticaria, angioedema or life-threatening events were observed. Conclusions: These preliminary data showed that various induction regimens for SLIT are generally well tolerated and could allow a fast build-up phase of SLIT.

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Low zone tolerance (LZT) to contact allergens is induced by epicutaneous exposure to haptens in subsensitizing doses resulting in an inhibition of contact hypersensitivity (CHS), which, in contrast, occurs after sensitization with immunogenic doses of allergens. Performing the protocol of tolerance induction resulted in robust LZT to allergens in B cell-deficient mice in vivo, indicating that B cells are not required for the induction and effector phase of LZT. However, CHS reactions in vivo were restricted in B cell-deficient mice as compared to wild-type (WT) mice. In contrast, analysis of hapten-specific T cell activation in vitro revealed a strong proliferative response of T cells derived from both WT and B celldeficient sensitized mice. Similar to WT animals, T cells obtained from tolerized B celldeficient mice produced a Tc2 cytokine pattern of LZT with high levels of IL-4 and IL-10, whereas sensitization of B cell-deficient mice resulted in the typical Tc1 cytokine profile of CHS. Adoptive transfer of CD8 + effector T cells from tolerized or sensitized B cell-deficient mice induced significant LZT or CHS reactions, respectively, in WT recipients, demonstrating that the development of hapten-specific effector CD8 + T cells of LZTand CHS is independent of B cells.

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