title: On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs.
abstract: We have investigated the interaction between DR1 molecules and the two antigenic peptides, tetanus toxoid 830-843 and hemagglutinin 307-319, previously known to bind most DR alleles (degenerate binding) and to be recognized by the same T cell clones in the context of different DR alleles (promiscuous T cell recognition). The DR1 affinity of these two peptides was compared with that of two other different T cell epitopes (pertussis toxin 30-42 and ragweed allergen Ra3 51-65). It was found that degeneracy and promiscuity were associated with high affinity interactions, whereas binding and T cell selectivity were associated with weaker interactions. Thus, the selectivity of DR-peptide interactions, as is commonly observed with the antibody molecule, appears to be inversely correlated to affinity. Several singly substituted analogs of the hemagglutinin 307-319 determinant have also been tested for capacity to bind various DR alleles (DR1, DR2, DR5, and DR7). The results obtained suggest that this determinant may bind the different DR alleles in a similar orientation. Similar conclusions were reached when the interaction between the tetanus toxoid 830-843 determinant and three different DR alleles (DR1, DR2, and DR7) was studied following the same experimental approach. When crucial DR-binding residues of the two peptides were compared, it was found that they were very similar in both chemical nature and spacing in the peptide primary structure, suggesting that the two peptides may bind DR in a very similar orientation. Finally, a putative motif has been derived and shown to be present in a majority of the DR binders tested, but only in a minority of the non-DR binding peptides.
authors.affiliation: Cytel, San Diego, CA 92121.
authors.forename: D
authors.initials: D
authors.lastname: O'Sullivan
authors.forename: T
authors.initials: T
authors.lastname: Arrhenius
authors.forename: J
authors.initials: J
authors.lastname: Sidney
authors.forename: M F
authors.initials: MF
authors.lastname: Del Guercio
authors.forename: M
authors.initials: M
authors.lastname: Albertson
authors.forename: M
authors.initials: M
authors.lastname: Wall
authors.forename: C
authors.initials: C
authors.lastname: Oseroff
authors.forename: S
authors.initials: S
authors.lastname: Southwood
authors.forename: S M
authors.initials: SM
authors.lastname: Colón
authors.forename: F C
authors.initials: FC
authors.lastname: Gaeta
mesh_terms: D000483:Alleles; D001665:Binding Sites; D002460:Cell Line; D000939:Epitopes; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D006388:Hemagglutinins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013745:Tetanus Toxoid / Q000378:metabolism*
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D006388:Hemagglutinins; D010446:Peptide Fragments; D013745:Tetanus Toxoid