Skip to main content

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

Publication ,  Journal Article
Nair, S; Wearsch, PA; Mitchell, DA; Wassenberg, JJ; Gilboa, E; Nicchitta, CV
Published in: J Immunol
June 1, 1999

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.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

June 1, 1999

Volume

162

Issue

11

Start / End Page

6426 / 6432

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • T-Lymphocytes, Cytotoxic
  • Ribonucleoproteins
  • Protein Binding
  • Peptides
  • Ovalbumin
  • Molecular Chaperones
  • Mice, SCID
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
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. J Immunol, 162(11), 6426–6432.
Nair, S., P. A. Wearsch, D. A. Mitchell, J. J. Wassenberg, E. Gilboa, and C. V. Nicchitta. “Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides.J Immunol 162, no. 11 (June 1, 1999): 6426–32.
Nair S, Wearsch PA, Mitchell DA, Wassenberg JJ, Gilboa E, Nicchitta CV. Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides. J Immunol. 1999 Jun 1;162(11):6426–32.
Nair, S., et al. “Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides.J Immunol, vol. 162, no. 11, June 1999, pp. 6426–32.
Nair S, Wearsch PA, Mitchell DA, Wassenberg JJ, Gilboa E, Nicchitta CV. Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides. J Immunol. 1999 Jun 1;162(11):6426–6432.

Published In

J Immunol

ISSN

0022-1767

Publication Date

June 1, 1999

Volume

162

Issue

11

Start / End Page

6426 / 6432

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • T-Lymphocytes, Cytotoxic
  • Ribonucleoproteins
  • Protein Binding
  • Peptides
  • Ovalbumin
  • Molecular Chaperones
  • Mice, SCID
  • Mice, Inbred C57BL
  • Mice