© The Rockefeller University Press, 0022-1007/1999/3/797/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 5, March 1, 1999 797-802
Calreticulin, a Peptide-binding Chaperone of the Endoplasmic Reticulum, Elicits Tumor- and Peptide-specific Immunity
Sreyashi Basu and
Pramod K. Srivastava
From the Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, Connecticut 06030
Calreticulin (CRT), a peptide-binding heat shock protein (HSP) of the endoplasmic reticulum (ER), has been shown previously to associate with peptides transported into the ER by transporter associated with antigen processing (Spee, P., and J. Neefjes. 1997. Eur. J. Immunol. 27: 2441–2449). Our studies show that CRT preparations purified from tumors elicit specific immunity to the tumor used as the source of CRT but not to an antigenically distinct tumor. The immunogenicity is attributed to the peptides associated with the CRT molecule and not to the CRT molecule per se. It is further shown that CRT molecules can be complexed in vitro to unglycosylated peptides and used to elicit peptide-specific CD8+ T cell response in spite of exogenous administration. These characteristics of CRT closely resemble those of HSPs gp96, hsp90, and hsp70, although CRT has no apparent structural homologies to them.
Key Words: heat shock protein stress protein antigen presentation cytotoxic T lymphocyte response cancer immunity
Address correspondence to Pramod K. Srivastava, Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, MC1601, Farmington, CT 06030. Phone: 860-679-4444; Fax: 860-679-4365; E-mail: srivastava{at}nso2.uchc.edu
Note added in proof. During the course of these studies, we have learned that C. Nicchita, E. Gilboa, and colleagues have independently discovered that calreticulin can elicit, in a cell- and tumor-specific manner, CTL responses (Nair, S., P. Wearsch, D.A. Mitchell, J.J. Wassenberg, E. Gilboa, and C.V. Nicchita. Calreticulin displays in vivo peptide binding activity and can elicit cytotoxic T lymphocyte responses against bound peptides. J. Immunol. In press.).
Abbreviations used: CRT, calreticulin; ER, endoplasmic reticulum; HSP, heat shock protein; PDI, protein disulfide isomerase; TAP, transporter associated with antigen processing; VSV, vesicular stomatitis virus.

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