Background: Peptide immunotherapy is a promising alternative for treating allergic diseases. One way to enhance the efficacy of peptide immunotherapy is to use altered peptide ligands (APLs) that contain amino acid substitutions compared with the natural peptide.
Objective: To evaluate the potential of an APL of the immunodominant epitope of lipocalin allergen Bos d 2 for peptide immunotherapy.
Methods: Peripheral blood CD4(+) T-cell responses of 8 HLA-DR4-positive subjects to the natural ligand of Bos d 2 (p127-142) or to an APL (pN135D) were analyzed by MHC class II tetramer staining after in vitro expansion with the peptides. Long-term T-cell lines (TCLs) were induced with the peptides, and the cytokine production, cross-reactivity, and T-cell receptor Vbeta subtype expression of the TCLs were analyzed.
Results: CD4(+) T cells specific for both p127-142 and pN135D were readily detected in peripheral blood after a single in vitro stimulation. Whereas the TCLs induced with p127-142 were T(H)2/T(H)0-deviated, those induced with pN135D were T(H)1/T(H)0-deviated and highly cross-reactive with p127-142. Moreover, the pN135D-induced TCLs appeared to use a broader repertoire of T-cell receptor Vbeta subtypes than those induced with p127-142.
Conclusion: An APL of an immunodominant allergen epitope was able to induce a novel T(H)1-deviated T-cell population cross-reactive with the natural epitope in vitro. This cell population could have a therapeutic immunomodulatory function in vivo through bystander suppression.
Clinical implications: These results support the idea that altered peptide ligands may be used to enhance the efficacy of peptide immunotherapy.