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.