Inefficient exogenous loading of a tapasin-dependent peptide onto HLA-B*44:02 can be improved by acid treatment or fixation of target cells

V. Stroobant, N. Demotte, R. M. Luiten, R. M. Leonhardt, P. Cresswell, Aude Bonehill, A. Michaux, W. Ma, A. Mulder, B.j. Van Den Eynde, Pierre Van Der Bruggen, N. Vigneron

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Antitumor cytolytic T lymphocytes (CTLs) recognize peptides derived from cellular proteins and presented on MHC class I. One category of peptides recognized by these CTLs is derived from proteins encoded by "cancer-germline" genes, which are specifically expressed in tumors, and therefore represent optimal targets for cancer immunotherapy. Here, we identify an antigenic peptide, which is derived from the MAGE-A1-encoded protein (160-169) and presented to CTLs by HLA-B*44:02. Although this peptide is encoded by MAGE-A1, processed endogenously and presented by tumor cells, the corresponding synthetic peptide is hardly able to sensitize target cells to CTL recognition when pulsed exogenously. Endogenous processing and presentation of this peptide is strictly dependent on the presence of tapasin, which is believed to help peptide loading by stabilizing a peptide-receptive form of HLA-B*44:02. Exogenous loading of the peptide can be dramatically improved by paraformaldehyde fixation of surface molecules or by peptide loading at acidic pH. Either strategy allows efficient exogenous loading of the peptide, presumably by generating or stabilizing a peptide-receptive, empty conformation of the HLA. Altogether, our results indicate a potential drawback of short peptide-based vaccination strategies and offer possible solutions regarding the use of problematic epitopes such as the one described here.
Original languageEnglish
Pages (from-to)1417-1428
Number of pages12
JournalEuropean Journal of Immunology
Volume6
Issue number42
Publication statusPublished - Jun 2012

Keywords

  • peptide
  • HLA
  • HLA-B*44:02
  • target cells
  • acid

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