G Toussaint

Major T cell epitope-containing peptides can elicit strong antibody responses

Peptides containing major T cell epitopes have the capacity to induce T cell anergy and have therefore been proposed for the treatment of allergic and autoimmune diseases. Such peptides should not be immunogenic, i.  e. should not contain a B cell recognition site. We have evaluated in BALB / c mice the therapeutic potential of a 15‐mer peptide (p21 – 35) derived from Der p2, a major allergen of the house dust mite Dermatophagoides pteronyssinus, which contains a dominant T cell epitope but is not recognized by antibodies to Der p2. Unexpectedly, p21 – 35 elicited strong immune responses, suggesting the presence of a cryptic B cell epitope. Similar results were obtained with mice of three additional MHC haplotypes. A core sequence of four amino acids (Ile‐Ile‐His‐Arg) corresponding to residues 28 – 31 was shared by the B and T cell epitopes. Critical residues for B cell recognition were Arg31 and Lys33, while Ile28 was essential for T cell recognition. A Lys33Ala mutant of p21 – 35 still activated T cells but had much reduced immunogenic properties, making it a suitable alternative peptide for T cell anergy induction. Careful investigation of the immunogenic potential of peptides used to induce T cell anergy should be carried out prior to their clinical application.

Occupational asthma caused by sarsaparilla root dust

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Reduced exercise capacity in a mouse model of asthma

One of the important clinical features of asthma is the exercise intolerance due to an exacerbation.1 Yet, to our knowledge, this end point has never been assessed in animal models of asthma. In a mouse model of chemical induced asthma we found early and late alterations in ventilatory function using unrestrained whole body plethysmography.2–4 Partly because this technique has been heavily criticised,5 we sought to provide another measure of functional impairment in asthma—namely, exercise endurance. This was done by a simple exercise test in which mice were forced to swim against a limited downwards current;6 if they stopped swimming the current pulled them under the water. Swimming endurance time is measured as a proxy of exercise tolerance. Task failure is defined as a period of 5 seconds under water.6 The protocol for sensitising and challenging mice was similar to that used previously,2–4 with small modifications. Male BALB/c mice (±20 g, 6 weeks old) received dermal applications of 20 µl vehicle (2:3 …