T-cell receptor contact and MHC binding residues of a major rye grass pollen allergen T-cell epitope.

Abstract

T cells are pivotal in the elicitation of allergic diseases. Analogues of T-cell epitope peptides with a modification at a T-cell receptor (TCR) contact site can alter selected T-cell effector functions. Thus the ability to modulate allergen-specific T-cell responses towards TH1 -like by stimulation with peptide analogues may downregulate allergic inflammation. The purpose of this study was to characterize the minimal epitope recognized by cloned T cells of a dominant Lol p 5 epitope, p105-116, and identify the critical residues involved in TCR and MHC contact. Using peptides with progressive truncation of N- and C-terminal residues in T-cell proliferation assays, we identified the core epitope recognized by cloned CD4(+) T cells. An additional series of peptides with single amino acid substitutions were used in T-cell proliferation and live-cell MHC binding assays. Taken together, these results allowed identification of MHC binding and TCR contact residues of p105-116. The core epitope of p105-116 was identified as residues 107-114. Within this core epitope, 3 residues were found to be important for MHC binding, positions 107, 110, and 112, whereas those at positions 108, 109, 110, 111, and 113 were putative TCR contact residues. The identification of the TCR and MHC contact residues of a dominant Lol p 5 T-cell epitope and analogues of this peptide capable of modulating T-cell responses will allow the evaluation of these peptides' potential as immunotherapeutic agents for rye grass pollen allergic disease.