MOST cytotoxic T lymphocytes (CTL) recognize epitopes of foreign viral proteins in association with class I major histo-compatibility complex (MHC) molecules1. Viral proteins synthesized in the cytoplasm require intracellular fragmentation and exposure to the class I antigens for the development of CTL responses2–4. Although indirect evidence for binding of peptides to class I antigens has accumulated, direct binding has only been shown recently5,6. The formation of complexes between peptide and class I antigen may occur in the endoplasmic reticulum (ER)7,8 and peptides have been shown to induce assembly of the class I complex9. We have translated the messenger RNAs encoding HLA-B27 (subtype 2705)10,11 and 02-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 nucleoprotein12 (residues 384–394) of influenza A virus. This peptide induces CTL activity against target cells expressing the HLA-B27 antigen13. Here we report direct evidence that the nucleoprotein peptide promotes assembly of the HLA-B27 heavy chain and β2-microglobulin, and that this can occur in the ER immediately after synthesis of the two proteins.
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Kvist, S., Hamann, U. A nucleoprotein peptide of influenza A virus stimulates assembly of HLA-B27 class I heavy chains and β2-micro-globulin translated in vitro. Nature 348, 446–448 (1990). https://doi.org/10.1038/348446a0
Proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation
Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules