Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides

Smita Nair, Pamela A. Wearsch, Duane A. Mitchell, James J. Wassenberg, Eli Gilboa, Christopher V. Nicchitta

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Calreticulin is an endoplasmic reticulum (ER) chaperone that displays lectin activity and contributes to the folding pathways for nascent glycoproteins. Calreticulin also participates in the reactions yielding assembly of peptides onto nascent MHC class I molecules. By chemical and immunological criteria, we identify calreticulin as a peptide-binding protein and provide data indicating that calreticulin can elicit CTL responses to components of its bound peptide pool. In an adoptive immunotherapy protocol, dendritic cells pulsed with calreticulin isolated from B16/F10.9 murine melanoma, E.G7-OVA, or EL4 thymoma tumors elicited a CTL response to as yet unknown tumor-derived Ags or the known OVA Ag. To evaluate the relative efficacy of calreticulin in eliciting CTL responses, the ER chaperones GRP94/gp96, BiP, ERp72, and protein disulfide isomerase were purified in parallel from B16/F10.9, EL4, and E.G7-OVA tumors, and the capacity of the proteins to elicit CTL responses was compared. In both the B16/F10.9 and E.G7-OVA models, calreticulin was as effective as or more effective than GRP94/gp96 in eliciting CTL responses. Little to no activity was observed for BiP, ERp72, and protein disulfide isomerase. The observed antigenic activity of calreticulin was recapitulated in in vitro experiments, in which it was observed that pulsing of bone marrow dendritic cells with E.G7-OVA-derived calreticulin elicited sensitivity to lysis by OVA-specific CD8+ T cells. These data identify calreticulin as a peptide-binding protein and indicate that calreticulin-bound peptides can be re-presented on dendritic cell class I molecules for recognition by CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)6426-6432
Number of pages7
JournalJournal of Immunology
Volume162
Issue number11
StatePublished - Jun 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nair, S., Wearsch, P. A., Mitchell, D. A., Wassenberg, J. J., Gilboa, E., & Nicchitta, C. V. (1999). Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides. Journal of Immunology, 162(11), 6426-6432.