Subcellular localization of the melanoma-associated protein Melan-AMART-1 influences the processing of its
D Rimoldi1, K Muehlethaler, S Salvi
1Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland. Donata.Rimoldi@isrec.unil.ch
The peptide derived from the melanoma-associated protein Melan-A (Melan-A(26-35)/HLA-A2) is an attractive candidate for tumor immunotherapy but little is known about the intracellular processing of this antigen. Here we show that Melan-A is a single-pass membrane protein with an NH(2) terminus exposed to the lumen of the exocytic compartment. In transfected melanoma cells, Melan-A accumulates in the Golgi region. Inversion of the membrane topology leads to the retention of Melan-A in the endoplasmic reticulum. Most strikingly, melanoma cells expressing this form of Melan-A are more effectively recognized by specific CTL than those expressing either Melan-A in its native membrane orientation or Melan-A artificially localized in the cytosol. Our data are compatible with the notion that proteins retained in the endoplasmic reticulum are more efficiently degraded and produce more antigenic peptides.
The peptide derived from the melanoma-associated protein Melan-A (Melan-A(26-35)/HLA-A2) is an attractive candidate for tumor immunotherapy but little is known about the intracellular processing of this antigen. Here we show that Melan-A is a single-pass membrane protein with an NH(2) terminus exposed to the lumen of the exocytic compartment. In transfected melanoma cells, Melan-A accumulates in the Golgi region. Inversion of the membrane topology leads to the retention of Melan-A in the endoplasmic reticulum. Most strikingly, melanoma cells expressing this form of Melan-A are more effectively recognized by specific CTL than those expressing either Melan-A in its native membrane orientation or Melan-A artificially localized in the cytosol. Our data are compatible with the notion that proteins retained in the endoplasmic reticulum are more efficiently degraded and produce more antigenic peptides.
