Selective export of MHC class I molecules from the ER after their dissociation from TAP

It has been assumed that upon dissociation from TAP, MHC class I molecules exit the ER by nonselective bulk flow. We now show that exit must occur by association with cargo receptors. Inconsistent with exit by bulk flow, load ing of MHC class I molecules with high-affinity peptides triggers dissociat ion from TAP but has no effect on rates of ER-to-Golgi transport. Moreover, peptide-loaded MHC class I molecules accumulate at ER exit sites from whic h TAP molecules are excluded. Consistent with receptor-mediated exit, ER-to -Golgi transport of MHC class I molecules is independent of their cytoplasm ic tails, which themselves lack ER export motifs. In addition, we show that MHC class I molecules associate with the putative cargo receptor BAP31.