Efficient loading of identical viral peptide onto class II molecules by antigenized immunoglobulin and influenza virus.
Several prior reports have identified peptides that are naturally associated with major histocompatibility complex (MHC) class II molecules on presenting cells. We have examined the delivery of a peptide from exogenous sources to MHC class II molecules. The peptide derives from the influenza virus hemagglutinin (HA) and activates a CD4+ T cell hybridoma. In functional assays of antigen presentation, this epitope is delivered effectively to T cells either in the context of influenza virus or chimeric immunoglobulin (Ig) molecules (Ig-HA) in which the peptide has replaced the CDR3 loop of the heavy chain. We find that the identical 11-mer peptide can be isolated from mouse MHC class II antigens whether the exogenous source of peptide is free HA peptide, the Ig-HA chimera, or ultraviolet-inactivated PR8 influenza virus. The Ig-HA chimera proves to be the most efficient vehicle for charging class II molecules via the exogenous route. Given the fact that self Igs represent natural long-lived carriers, we suggest that antigenized Igs have considerable potential for peptide delivery to MHC molecules in situ.
Brumeanu
T D
TD
Department of Microbiology, Mount Sinai School of Medicine, New York 10029.
Swiggard
W J
WJ
Steinman
R M
RM
Bona
C A
CA
Zaghouani
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000528:radiation effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D009980:Influenza A virus / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins