Major histocompatibility complex class I-restricted presentation of influenza virus nucleoprotein peptide by B lymphoma cells harboring an antibody gene antigenized with the virus peptide.
We analyzed the capacity of B cells to process and present a peptide from the variable region of an endogenous immunoglobulin heavy (H) chain to a major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocyte (CTL) clone. The H-chain gene was engineered to express 14-amino acid peptide from the sequence of the influenza virus nucleoprotein (NP) antigen in the third complementarity-determining region (CDR3). This NP peptide is presented in association with the Db allele in H-2b mice. We demonstrate that B lymphoma cells (H-2b) harboring the antigenized H-chain gene process and present the NP peptide in association with the Db molecule and are lysed by a CTL clone specific for that peptide in an MHC-restricted way. In contrast, the soluble antigenized antibody failed to mediate lysis of H-2b target cells. The endogenously processed immunoglobulin CDR3 peptide could be eluted from surface Db molecules in transfected cells. This study formally demonstrates that peptides from the hypervariable loops of endogenous immunoglobulin are processed through the endogenous degradative pathway and are presented to CD8+ T cells in the context of MHC class I molecules. The implication of these findings for processing and presentation of endogenous immunoglobulin peptides in B cells and network regulation by idiopeptides is discussed.
Billetta
R
R
Department of Medicine, University of California, San Diego, La Jolla 92093-0063, USA.
Filaci
G
G
Zanetti
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D004950:Esterases / Q000032:analysis; D006183:H-2 Antigens / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D016393:Lymphoma, B-Cell; D051379:Mice; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000276:immunology*
D006183:H-2 Antigens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009698:Nucleoproteins; D014758:Viral Core Proteins; D004950:Esterases