[Determination of a peptide deduced from the influenza virus haemagglutinin that induces human class II-restricted T cell responses in DQ6 transgenic mice].
HLA-DQ6 (DQ6) transgenic mice were immunized with a set of peptides deduced from either a fragment of the haemagglutinin (HA) of influenza A/Aichi/2/68 virus (HA123-138) or pigeon cytochrome c 43-58 (p43-58) analogues. HA123-138 induced a moderate level of T cell responses in DQ6 transgenic mice. The T cell responses were shown to be restricted to either the DQ6 or I-Ab molecule. We then established T cell hybridomas specific for HA123-138 and restricted to DQ6 from DQ6 transgenic mice immunized with the HA123-138. These T cell hybridomas were activated by the stimulation with HA123-138 in the presence of an HLA-DQ6 transfectant or a paraformaldehyde-fixed HLA-DQ6 positive EB cell line. Using one of these T cell hybridomas we searched for potent peptides which showed high antigenicity as compared with HA123-138. We found that a hybrid peptide antigen, 46F/HA126-134/54A, which was composed of HA126-134 and the I-Ab binding component (46F/54A) previously determined on p43-58 analogues evoked considerable responses in the HA123-138 specific T cell hybridoma. Competitive inhibition assay with this T cell hybridoma and direct binding assay using a DQ6 positive EB cell line or DQ6-transfected L cells showed consistently that the agretopic position 46 of the p43-58 analogues and hybrid peptide antigens was preserved among DQ6-restricted T cell responses and murine class II, I-A, restricted T cell responses. Phenylalanine (F) at the position 46 appeared to be a critical residue for binding to HLA-DQ6 as had been shown for binding to I-Ab.
Takami
K
K
Section of Pathology, Hokkaido University, Sapporo, Japan.
D000595:Amino Acid Sequence; D000818:Animals; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
D006683:HLA-DQ Antigens; C063831:HLA-DQ6 antigen; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D014765:Viral Vaccines