Cellular immunity is dependent on major histocompatibility complex (MHC) class I molecules enabling cytotoxic T cell recognition of malignant and infected cells. Loading of antigenic peptides onto MHC class I is assisted by a peptide-loading protein complex including tapasin. We found that tapasin expression is enhanced by beta 2-microglobulin via both transcriptional and post-transcriptional mechanisms. In addition, using conditions which preserve the tapasin-ERp57 disulfide-bonded conjugate, we demonstrated that beta 2-microglobulin increases tapasin-containing protein complexes, and reduces the level of MHC class I/ERp57 complexes lacking tapasin. Overall, our results provide a new perspective on the regulation of tapasin expression and association.