A nucleoprotein peptide of influenza A virus stimulates assembly of HLA-B27 class I heavy chains and beta 2-microglobulin translated in vitro.
Most cytotoxic T lymphocytes (CTL) recognize epitopes of foreign viral proteins in association with class I major histocompatibility complex (MHC) molecules. Viral proteins synthesized in the cytoplasm require intracellular fragmentation and exposure to the class I antigens for the development of CTL responses. Although indirect evidence for binding of peptides to class I antigens has accumulated, direct binding has only been shown recently. The formation of complexes between peptide and class I antigen may occur in the endoplasmic reticulum (ER) and peptides have been shown to induce assembly of the class I complex. We have translated the messenger RNAs encoding HLA-B27 (subtype 2705) and beta 2-microglobulin in a rabbit reticulocyte lysate supplemented with human microsomal membranes (to mimic ER membranes), in the absence and presence of a peptide derived from the nucleoprotein (residues 384-394) of influenza A virus. This peptide induces CTL activity against target cells expressing the HLA-B27 antigen. Here we report direct evidence that the nucleoprotein peptide promotes assembly of the HLA-B27 heavy chain and beta 2-microglobulin, and that this can occur in the ER immediately after synthesis of the two proteins.
Kvist
S
S
Ludwig Institute for Cancer Research, Stockholm, Sweden.
Hamann
U
U
D002451:Cell Compartmentation; D002474:Cell-Free System; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology*; D046911:Macromolecular Substances; D008861:Microsomes / Q000378:metabolism; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments / Q000276:immunology*; D011499:Protein Processing, Post-Translational; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D014758:Viral Core Proteins / Q000276:immunology* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism*
D015796:HLA-B27 Antigen; D046911:Macromolecular Substances; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D014758:Viral Core Proteins; D001613:beta 2-Microglobulin