Use of antagonist peptides to inhibit in vitro T cell responses to Par j1, the major allergen of Parietaria judaica pollen.
Antigenic peptides with substituted side chains inhibit immune responses to a number of recall Ags from infectious agents in vitro. Here we show that the same strategy can be applied to peptides derived from a pollen protein, the major allergen of Parietaria judaica(Par j1), a plant responsible for most allergenic sensitization in the southern Mediterranean area. Three T cell lines responding to Par j1 protein were used to identify a stimulatory peptide. Two different monosubstituted altered peptide ligands (APL) were identified that bound to the HLA-DR of the responders, did not stimulate the T cell lines on their own, and decreased the response to subsaturating amounts of the unmodified stimulatory peptide. Most important, these APL were able to inhibit the response of these cell lines to intact Par j1 protein. A third monosubstituted peptide bound to the HLA-DR but did not show inhibitory activity. The two APL had a lower affinity than the unsubstituted peptide for the HLA-DR. The last two observations make MHC blockade an unlikely explanation for the observed effect. These results indicate the action of a specific peptide-mediated antagonism that may be useful in controlling the T cell component of an allergic response.
De Palma
R
R
Dipartimento di Internistica Clinica e Sperimentale II Universita' di Napoli, Italy.
Wu
S
S
Sallusto
F
F
Di Felice
G
G
Martucci
P
P
Geraci
D
D
Colombo
P
P
Troise
C
C
Sacerdoti
G
G
Nocera
A
A
Gorski
J
J
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D010940:Plant Proteins; D011058:Pollen / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*