The Role of Antigen Cross-presentation From Leukemia Blasts on Immunity to the Leukemia-associated Antigen PR1

• DOI: 10.1097/cji.0b013e31824b3b14
• Publication Date: 2012-04-10T19:29:56Z
• Authors: Gheath Alatrash; Yoko Ono; Anna Sergeeva; Pariya Sukhumalch...; Mao Zhang; Lisa S. St John; Tian-Hui Yang; Kathryn Ruisaard; Paul M. Armistead; Elizabeth A. Mitt...; Hong He; Na Qiao; Tania Rodriguez-Cruz; Shoudan Liang; Karen Clise-Dwyer; Eric D. Wieder; Gregory Lizee; Sijie Lu; Jeffrey J. Molldrem
• Keywords: Cross-Presentation; Antigen processing

Cross-presentation is an important mechanism by which exogenous tumor antigens are presented to elicit immunity. Because neutrophil elastase (NE) and proteinase-3 (P3) expression increased in myeloid leukemia, we investigated whether NE P3 cross-presented dendritic cells (DC) B cells, the source determines immune outcomes. We show that elevated leukemia patient serum levels correlate with remission status. demonstrate cellular uptake of into lysosomes, ubiquitination, proteasome processing for cross-presentation. Using anti-PR1/human leukocyte antigen-A2 monoclonal antibody, provide direct evidence B-cells cross-present soluble leukemia-associated P3, whereas DCs only P3. occurred at early time points but was not associated DC or B-cell activation, suggesting cross-presentation may favor tolerance. Furthermore, aberrant subcellular localization blasts compartments share common elements classic major histocompatibility class I antigen-presenting pathway, facilitate Our data distinct mechanisms cell-associated be valuable understanding immunity PR1 leukemia.