Immunization of BALB/c mice with peptide HVSGHRMAWDMMMNWA, encompassing residues 121-135 from hepatitis C virus E1 protein, induced CD4 ⍣ T h 1 cells as well as a long-lasting CD8 ⍣ cytotoxic T lymphocyte (CTL) response in vivo when the peptide was administered s.c. with or without incomplete Freund's adjuvant. Using truncated peptides from this sequence it was shown that the determinant recognized by cytotoxic T cells was encompassed by residues SGHRMAWDM. Deletion of residues from the N-terminus or the C-terminus of the wild-type peptide abrogated its helper character. When Val122 of the wild peptide was replaced by Ala, the ability to induce a cytotoxic response was lost concomitantly with the loss of the T h 1 pattern of cytokine production. Interestingly, the Ala-modified peptide, when co-immunized with a peptide encompassing residues 323-329 from ovalbumin (OVA), which is able to induce a T h 1 response in BALB/c mice, restored the capacity of the modified peptide to induce CTL. However, co-immunization of the Ala-modified peptide with a peptide encompassing residues 106-118 from sperm whale myoglobin, which induces a T h 0 cytokine profile in BALB/c mice, was much less efficient than the OVA peptide to restore CTL induction. These results demonstrate that CTL induction with a short synthetic peptide requires that this peptide contains domains recognized by T c cells as well as by T h 1 cells. For those peptides that do not contain this type of T h domain, competent T cell help can be provided by co-immunization with a distinct peptide that is able to stimulate a T h 1 response.

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Summary Pemphigus vulgaris is a blistering skin disorder, which can be severe. Antibodies are a type of protein used by the immune system when fighting off disease or infection, but they can sometimes turn against healthy cells. People with pemphigus vulgaris develop antibodies to various proteins that cement certain skin cells (epidermal cells) together, these include desmoglein 1, desmoglein 3 and desmocollin, together with other unidentified proteins. The damage caused by these antibodies causes separation of epidermal cells, visible under the microscope (and known as acantholysis), eventually resulting in blister formation. The antibodies may act directly on these proteins or indirectly by activation of other inflammatory substances including a disintegrin and metalloproteinase 10 (ADAM10). The authors, based in Pamplona, northern Spain, aimed to see if blistering induced by different antibodies in patients with pemphigus vulgaris involved activation of ADAM10. They found that antibodies to desmocollin triggered early splitting of the skin, independent of ADAM10. The timing and severity of splitting of skin cells induced by desmoglein antibodies 1 and 3, however, was dependent on the level of antibodies and also on activation of ADAM10. In these, inhibition of ADAM10 prevented acantholysis. The authors propose a role for development of ADAM10 inhibitors in the treatment of the subgroup of patients with pemphigus vulgaris who have antibodies to desmogleins 1 and 3. This is a summary of the study: The involvement of ADAM10 in acantholysis in mucocutaneous pemphigus vulgaris depends on the autoantibody profile of each patient.

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