title: Binding of ALA-substituted analogs of HA306-320 to DR1101, DR1301, and DR0402 molecules: correlation of DR-peptide interactions with recognition by a single TCR.
abstract: We tested the hypothesis that a cross-reactive T-cell clone could recognize HA306-320 peptide complexed to autologous HLA-DR1101, and also to allogenic HLA-DR0402 and HLA-DR1301 molecules, because of similar orientations of HA306-320 side chains in the groove of the three DR molecules. To approach peptide orientations in each HLA groove we compared the capacity of Ala-monosubstituted analogs to bind and be presented by DR1101, DR0402, and DR1301. Results indicated that the orientation of HA306-320 in DR1101 was grossly similar to the known orientation of HA307-319 in DR0101. Data suggested many similarities in peptide orientations in DR0402 and DR1301 as well. However, differences in binding were also observed. Ala substitution of Y309 had much less effect on peptide binding to DR1301 and DR0402 than to DR1101 and Ala-substitution of T314 increased affinity for DR1301 but not for DR1101 and DR0402. These alterations of peptide-DR interactions were probably communicated to the upper peptide surface. Indeed, the levels of T-cell clone reactivities against analogs mutated at positions predicted to face the TCR were lower when complexed to allogeneic DR molecules than when complexed to DR1101. Yet these epitopic alterations are likely subtle, since the decreased reactivity of the clone to allogeneic molecules could be compensated by peptide substitution at Y309, predicted to face the MHC.
authors.affiliation: Laboratoire du développement et de la maturation du système immunitaire, Hôpital Robert Debré, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Zeliszewski
authors.forename: J J
authors.initials: JJ
authors.lastname: Golvano
authors.forename: P
authors.initials: P
authors.lastname: Gaudebout
authors.forename: I
authors.initials: I
authors.lastname: Dorval
authors.forename: F
authors.initials: F
authors.lastname: Borras-Cuesta
authors.forename: G
authors.initials: G
authors.lastname: Sterkers
mesh_terms: D000409:Alanine / Q000032:analysis*; D000595:Amino Acid Sequence; D003429:Cross Reactions / Q000276:immunology; D006684:HLA-DR Antigens / Q000378:metabolism*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology / Q000378:metabolism; D006388:Hemagglutinins / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000032:analysis*; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006388:Hemagglutinins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D007930:Leucine; D000409:Alanine