HLA-A*0201 presents TAP-dependent peptide epitopes to cytotoxic T lymphocytes in the absence of tapasin.
Tapasin is a 48-kDa endoplasmic reticulum (ER)-resident glycoprotein that binds to the transporter associated with antigen processing (TAP) and mediates an interaction between TAP and newly synthesized MHC class I molecules. It is also essential for the proper antigen presenting function of HLA-A*0101 (HLA-A1), HLA-A*0801 (HLA-B8) and HLA-B*4402 (HLA-B4402). We show here that while tapasin is required for HLA-A*0201 (HLA-A2) molecules to bind to TAP, its absence does not block the presentation of HLA-A2-restricted TAP-dependent epitopes to cytotoxic T lymphocytes indicating that, unlike HLA-A1, HLA-B8 and HLA-B4402, HLA-A2 has access to the TAP-dependent peptide pool even in the absence of tapasin. Nevertheless, the overall efficiency with which HLA-A2 was loaded with optimal, stabilizing peptides was impaired in the cell line .220, resulting in a significant increase in the fraction of HLA-A2 molecules being released from the ER in a "peptide-receptive" state.
Lewis
J W
JW
Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, GB.
Sewell
A
A
Price
D
D
Elliott
T
T
D017951:Antigen Presentation / Q000276:immunology*; D017920:Antiporters / Q000276:immunology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D026901:Membrane Transport Proteins; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D017920:Antiporters; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin