PROTEIN DISULFIDE-ISOMERASE IS THE DOMINANT ACCEPTOR FOR PEPTIDES TRANSLOCATED INTO THE ENDOPLASMIC-RETICULUM

Peptides derived from cytosolic protein degradation are translocated i nto the lumen of the endoplasmic reticulum (ER) by the transporter ass ociated with antigen processing (TAP). In the ER, class I molecules bi nd the peptides fitting to their respective motifs and present them on the cell surface to CD8(+) T lymphocytes. However, most TAP-transloca ted peptides are not expected to bind to the class I molecules present in a particular cell. Recently, we have demonstrated that TAP-translo cated peptides containing a photoreactive phenylalanine analogue can b e cross-linked to two luminal ER-resident proteins: with low efficienc y to the stress protein gp96 and with high efficiency to a 60-kDa prot ein (Lammert, E. et al., Eur. J. Immunol. 1997. 27: 923). Both protein s have also been labeled specifically by TAP-translocated peptides con jugated to a different photoreactive group (Marusina, K. et al., Bioch emistry 1997. 36: 856). Here, we show that the 60-kDa peptide-binding protein is identical to the multifunctional protein disulfide isomeras e (PDI). Since PDI is the only luminal ER-resident protein that is lab eled by the photoreactive peptides with high efficiency, it might repr esent the dominant acceptor for TAP-translocated peptides.