70 kDa heat shock cognate protein is a transformation-associated antigen and a possible target for the host's anti-tumor immunity.

Abstract

We previously investigated a novel heat-inducible transformation-associated cell surface Ag that is expressed on the activated H-ras oncogene-transformed rat fibrosarcoma W31, but not its parental nontransformed fibroblast WFB. This Ag was detected by mAb 067. Herein, we characterized the molecular nature of the Ag by using anti-heat shock protein (HSP) mAb. The accumulated data indicated that the cell surface expression of Ag was clearly enhanced by several stressors, such as TNF, L-azetidine-2-carboxylic acid, and sodium arsenite. The immunoprecipitate made with mAb 067 and W31 cell lysates reacted with anti-rat 70 kDa heat shock cognate (HSC) mAb, TG5E, indicating that 067-defined Ag may be a rat 70 kDa HSC. Because this Ag seemed to be one of the transformation-associated Ag of WFB, we further studied whether it could play an important role in the host's anti-tumor immunity. Peripheral T cells of rats primed with live BCG showed cytotoxicity to W31 but not to WFB. Because the possibility existed that HSP may interact with certain populations of T cells, we focused on the reactivity of CD4-CD8- double negative T (DNT) cells against 067-defined molecule. DNT cells from spleen and PBL of live BCG-primed rats showed the cytotoxicity against W31 cells. This cytotoxicity was completely blocked by mAb 067 and anti-CD3 mAb. However, it was not blocked by mAb R48B1 and 109, which detect the MHC class I nonpolymorphic determinant and a target molecule of the cytolysis by poly I:C-induced NK cells, respectively. Furthermore, brefeldin A was able to block the cytotoxicity against W31 targets by DNT cells, but not by NK cells. These data suggest that 70 kDa HSC may be a tumor Ag and may act as a presenting molecule perhaps complexed with cellular peptides to certain DNT cells.

• Authors: Y Tamura, N Tsuboi, N Sato, K Kikuchi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 151 Issue 10 Pg. 5516-24 (Nov 15 1993) ISSN: 0022-1767 [Print] United States
• PMID: 8228242 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• Cyclopentanes
• Heat-Shock Proteins
• Brefeldin A

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Antigens, Neoplasm (analysis, immunology)
• Biological Transport
• Brefeldin A
• Cyclopentanes (pharmacology)
• Cytotoxicity, Immunologic
• Heat-Shock Proteins (analysis, immunology)
• Molecular Weight
• Neoplasms (immunology)
• Rats
• Rats, Inbred Strains
• T-Lymphocytes (immunology)