The role of antigen cross-presentation from leukemia blasts on immunity to the leukemia-associated antigen PR1

Gheath Alatrash, Yoko Ono, Anna Sergeeva, Pariya Sukhumalchandra, Mao Zhang, Lisa S. St John, Tian Hui Yang, Kathryn Ruisaard, Paul M. Armistead, Elizabeth A. Mittendorf, Hong He, Na Qiao, Tania Rodriguez-Cruz, Shoudan Liang, Karen Clise-Dwyer, Eric D. Wieder, Gregory Lizee, Sijie Lu, Jeffrey J. Molldrem

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)309-320
Number of pages12
JournalJournal of Immunotherapy
Issue number4
StatePublished - May 2012


  • cross-presentation
  • leukemia
  • myeloid
  • neutrophil elastase
  • PR1
  • proteinase-3

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology


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