T-cell receptor-mediated cross-allergenicity.

Background: Profilins are conserved and ubiquitous plant and animal proteins. We wanted to discover whether the T-cell response to conserved epitopes on birch and grass profilins could account for cross-allergenicity in subjects allergic to these two pollens.

Methods: Thirty-one patients allergic to grass and birch were recruited for the study. Grass and birch reactive T lymphocytes were studied by measuring proliferation to birch and grass allergen, respectively, followed by Vbeta T-cell receptor family-specific polymerase chain reaction and heteroduplex analysis. T-cell clones were derived from patients with cross-proliferating T cells.

Results: In 25 of 31 subjects the T-cell response to grass was quite distinct from that to birch. In contrast, in 6 of 31 individuals grass T cells cross-proliferated to birch and this was reproduced in 4 patients by birch profilin. CD4 Th2 cell clones were derived which promiscuously recognized homologously conserved regions on birch and grass profilins.

Conclusion: We conclude that a functionally relevant T-cell response to conserved regions of panallergens underlie cross-allergenicity in a subset of allergic patients. These results suggest that a reciprocal modulation of the response to one sensitizing allergen can occur following natural exposure to or immunotherapy with another allergen. These results have relevance in the management of patients with multiple allergies.