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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:103

Article

Burton, MD ; Blaher, B ; Suphioglu, C ; O'Hehir, RE ; Carbone, FR ; Rolland, JM

关键词: Lol p 5;    T-cell epitopes;    peptide analogues;    rye grass;    pollen allergen;    MHC class II;   

DOI  :  10.1016/S0091-6749(99)70499-9

来源: Elsevier

【 摘 要 】

Background: 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 T-H1-like by stimulation with peptide analogues may downregulate allergic inflammation. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

【 授权许可】

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