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

91 Citations (Scopus)

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

Fingerprint

Calreticulin
Peptides
Dendritic Cells
Protein Disulfide-Isomerases
Endoplasmic Reticulum
Carrier Proteins
T-Lymphocytes
Adoptive Immunotherapy
Neoplasms
Thymoma
Lectins
Bone Marrow Cells
Melanoma
Glycoproteins

ASJC Scopus subject areas

  • Immunology

Cite this

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.

Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides. / Nair, Smita; Wearsch, Pamela A.; Mitchell, Duane A.; Wassenberg, James J.; Gilboa, Eli; Nicchitta, Christopher V.

In: Journal of Immunology, Vol. 162, No. 11, 01.06.1999, p. 6426-6432.

Research output: Contribution to journalArticle

Nair, S, Wearsch, PA, Mitchell, DA, Wassenberg, JJ, Gilboa, E & Nicchitta, CV 1999, 'Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides', Journal of Immunology, vol. 162, no. 11, pp. 6426-6432.
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. Journal of Immunology. 1999 Jun 1;162(11):6426-6432.
Nair, Smita ; Wearsch, Pamela A. ; Mitchell, Duane A. ; Wassenberg, James J. ; Gilboa, Eli ; Nicchitta, Christopher V. / Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides. In: Journal of Immunology. 1999 ; Vol. 162, No. 11. pp. 6426-6432.
@article{0eb501c4b3e24a51898be28d226b38cf,
title = "Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides",
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.",
author = "Smita Nair and Wearsch, {Pamela A.} and Mitchell, {Duane A.} and Wassenberg, {James J.} and Eli Gilboa and Nicchitta, {Christopher V.}",
year = "1999",
month = "6",
day = "1",
language = "English",
volume = "162",
pages = "6426--6432",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides

AU - Nair, Smita

AU - Wearsch, Pamela A.

AU - Mitchell, Duane A.

AU - Wassenberg, James J.

AU - Gilboa, Eli

AU - Nicchitta, Christopher V.

PY - 1999/6/1

Y1 - 1999/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033152788&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033152788&partnerID=8YFLogxK

M3 - Article

VL - 162

SP - 6426

EP - 6432

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -