Factors controlling the trafficking and processing of a leader-derived peptide presented by Qa-1

Many leader-derived peptides require TAP for presentation by class I molecu les. This TAP dependence can either be ascribed to the inability of proteas es resident in the endoplasmic reticulum (ER) to trim leader peptide precur sors into the appropriate epitope or the failure of a portion of the leader segment to gain access to the lumen of the ER, Using the Qa-1 binding epit ope, Qdm derived from a class Is leader as a model, we show that many cell types lack ER protease activity to trim this peptide at its C terminus. How ever, both T1 and T2 cells contain appropriate protease activity to process the Full length D-d leader (DL) when introduced into the ER lumen. Neverth eless, both TI cells treated with the TAP inhibitor ICP47 and TAP(-) T2 cel ls fail to present this epitope from either the intact D-d molecule or a mi nigene encoding the DL, This indicates that the portion of the leader conta ining Qdm does not gain access to the ER, However, changing the Arg at P7 o f the DL to a Cys can alter its trafficking and allows for TAP-independent presentation of the Qdm epitope.