Tumor rejection antigens of chemically induced sarcomas of inbred mice.

Abstract

Chemically induced sarcomas of inbred mice are immunogenic in syngeneic hosts, and preimmunization with tumor cells leads to resistance to subsequent tumor transplants. The tumor rejection antigens (TRAs) that mediate this reaction are highly specific for each tumor; cross-protection between different syngeneic sarcomas is rare. Isolated membrane and cytosol fractions from two antigenically distinct BALB/c sarcomas, Meth A and CMS5, have TRA activity, and biochemical characterization of the active components from the cytosol and plasma membranes of these two tumors identified a glycoprotein ofMr 96,000. Immunization with unfractionated Meth A cytosol frequently leads to tumor enhancement, but the tumor-enhancing activity (TEA) is lost on fractionation and TRA activity becomes demonstrable. As Meth A and CMS5 lack expression of murine leukemia virus (MuLV) antigens or transcripts, MuLV-related antigens cannot be involved in the TEA or TRA activities of these tumors. In contrast to the lack of cross-reactivity between Meth A and CMS5 TRAs in transplantation tests, rabbit antiserum prepared against the Meth A Mr 96,000 antigen reacted with the CMS5 Mr 96,000 antigen. In view of the biochemical and antigenic similarities of Meth A and CMS5 TRAs, we propose that structurally related but distinct Mr 96,000 glycoproteins are expressed in chemically induced sarcomas and that these molecules are responsible for the individually specific immunogenicity of these tumors.

Do heat shock proteins have a role in breast cancer?

“…It has been demonstrated that inbred mice and rats immunised against their own tumours or tumours of the same genetic background become immune to challenges with tumour cells (Srivastava and Old, 1988 (Srivastava et al, 1986(Srivastava et al, , 1993Udono and Srivastava, 1993). However, it appears not to be the hsp itself that causes this immune response, rather the peptides that are attached to it.…”

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

“…The first reports of an immunological role for heat shock proteins (HSPs) were published over two decades ago (Srivastava et al 1986;Ullrich et al 1986) where it was shown that isolated HSPs when used as an immunogen protected syngeneic mice from the same tumour challenge and induced tumour-specific immunity. Since then, it has been reported that HSPs, including heat shock protein 70 (HSPA), were effective in cross-priming CD8 + T cells against the tumour from which these chaperones were isolated, recently reviewed by Srivastava (2002).…”

Cellular requirements for tumor-specific immunity elicited by heat shock proteins: tumor rejection antigen gp96 primes CD8+ T cells in vivo.

“…Heat shock proteins of 96-kDa size (gp96) have been suggested to mediate this antigenicity in the case of a number of methylcholanthrene-induced sarcomas (2-4) and a UV-induced fibrosarcoma (S. Janetzki, N. E. Blachere, and P.K.S., unpublished results). Administration of a purified gp% preparation renders mice resistant to the tumor from which gp% is isolated but not to an antigenically distinct tumor (2). In light of a lack of differences in the gp96 cDNA sequence among different tumors or among tumors and normal tissues, we suggested that the tumor-specific antigenicity of gp96 may derive not from gp96 per se but from low molecular weight peptides associated with gp% (5, 6).…”

“…Purification of gp96. gp96 was purified from Meth A cells as described (2). Briefly, a 60-ml pellet of Meth A cells was lysed in 240 ml of hypotonic buffer (30 mM NaHCO3/0.5 mM phenylmethylsulfonyl fluoride, pH 7.1) by Dounce homogenization, and a 100,000 x g supernatant was obtained.…”