Heat shock cognate protein 70 encodes antigenic epitopes recognised by HLA-B4601-restricted cytotoxic T lymphocytes from cancer patients

Abstract

Heat shock cognate protein 70 (HSC70), a highly conserved protein and a member of the family of molecular chaperones, has the ability to induce cytotoxic T lymphocyte (CTL) responses through binding and carrying antigenic peptides. We demonstrated in this study that the HSC70 gene encodes two antigenic peptides recognised by HLA-B46-restricted and tumour-reactive CTLs established from tumour-infiltrating lymphocytes of a colon cancer. These HSC70-derived peptides, at amino-acid positions 106 -114 and 233 -241, had the ability to induce HLA-B46-restricted and peptide-specific CTLs, which are reactive to tumour cells, from peripheral blood mononuclear cells of the majority of epithelial cancer patients tested. These results, along with those from the previous studies, indicate the two ways of HSC70 involvement in the immune responses to tumours: chaperones and antigens, and thus may provide a new insight for the development of HSC70-directed cancer-specific immunotherapy.

Hsp70 Translocates into the Plasma Membrane after Stress and Is Released into the Extracellular Environment in a Membrane-Associated Form that Activates Macrophages

“…Similarly, previous observations have shown that exosomes containing Hsp70 stimulated the cytosolic capacity of NK cells (17). Hsp70 has been found in serum obtained from patients suffering from an array of conditions, such as cancer (40,41), diabetes (42), coronary artery disease (43,44), myocardial infarction (45), and trauma (46). The presence of Hsp70 in circulation within membranes or in a free form still needs to be established.…”

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

“…Mutated and wild-type HSP70 proteins have been reported to be targets of CTLs (41)(42)(43), whereas other HSP family proteins have never been reported to be targets of immunocytes. HSP family proteins are often expressed in several kinds of normal organs, and immunocytes might be immunologically tolerated to those proteins.…”

Generation of Murine CTL by a Hepatitis B Virus-Specific Peptide and Evaluation of the Adjuvant Effect of Heat Shock Protein Glycoprotein 96 and Its Terminal Fragments

“…However, alum cannot efficiently switch on the innate responses and is thus unable to direct the adaptive immune responses. HSP70, another member of the HSP family, has been found to promote immunogenic APC function, elicit a strong CTL response, and prevent the induction of tolerance (45)(46)(47)(48)(49). Our results together with these previous findings point to the potential of using HSPs as a T cell adjuvant to induce CTLs targeting viral pathogens or cancer cells.…”