7 O - Relationship to multidrug resistance of the transporter associated with antigen presentation tap.

Multidrug resistance (MDR) has been related to two members of the ABC-superfamily of transporters, P-glycoprotein (Pgp) and Multidrug Resistance-associated Protein (MRP). We investigated the relationship of another ABC-transporter, the Transporter-associated with Antigen Presentation TAP, with MDR. TAP translocates peptides from the cytosol to the ER-Lumen where association with MHC class I molecules occurs. Using an anti-TAP antiserum on immunocytochemstry and Western blot, we found TAP overexpression in 5 of 8 MDR lines of different histogenetic origin. Reversion to drug sensitivity was associated with a decrease in TAP levels. Antiserum specificity was confirmed by using T1 (carrying TAP genes) and T2 (T1 mutant TAP-deficient) cells as controls. T1/T2 relative resistance to VP16, vincristine, and doxorubicin, was 2.33 ± 0.33, 1.7 ± 0.10, and 1.65 ± 0.07, respectively (p