A signal peptide derived from Hsp60 induces protective cytotoxic T lymphocyte immunity against lymphoid malignancies independently of TAP and classical MHC-I.

Abstract

Hsp60sp, a signal peptide derived from the leader sequence of heat shock protein 60 kDa (Hsp60), is a Qa-1/HLA-E-binding peptide. We previously showed that Hsp60sp-specific CD8+ T cells are involved in the immunoregulation of autoimmune diseases by controlling the response of self-reactive lymphocytes. Here, we report that Hsp60sp-specific CD8+ T cells killed malignant lymphocytes in vitro independently of transporter associated with antigen processing (TAP) and classical MHC-I expression. Induction of this cytotoxic T lymphocyte (CTL) response in vivo, either by adoptive transfer of in vitro-amplified CTLs or peptide-loaded dendritic cell immunization, resulted in effective control of lymphoid tumors, including TAP- or classical MHC-I-deficient cells. Hsp60sp-specific immune activation combined with programmed cell death protein 1 (PD-1) blocking synergistically restrained mouse lymphoma development. Importantly, Hsp60sp-specific CD8+ T cells did not negatively affect normal tissues and cells. Our data suggest that Hsp60sp-based immunotherapy is an inviting strategy to control lymphoid malignancies.

• Authors: Xun-Rui Chen, Hai-Hua Yuan, Jia-Hui Guo, Wen-Ying Zhang, Qian-Qian Li, Guo-Ding Huang, Yan-Jie Zhang, Bin Jiang, Feng Liu
• Journal: Cancer letters (Cancer Lett) Vol. 494 Pg. 47-57 (12 01 2020) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 32829008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Chaperonin 60
• Histocompatibility Antigens Class I
• Hspd1 protein, mouse
• Immune Checkpoint Inhibitors
• Mitochondrial Proteins
• Protein Sorting Signals

Topics

• Animals
• Antigen Presentation
• CD8-Positive T-Lymphocytes (immunology, transplantation)
• Cell Line
• Chaperonin 60 (chemistry, immunology)
• Combined Modality Therapy
• Dendritic Cells (immunology, transplantation)
• Female
• Histocompatibility Antigens Class I (metabolism)
• Immune Checkpoint Inhibitors (administration & dosage, pharmacology)
• Immunization
• Lymphoma (immunology, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mitochondrial Proteins (chemistry, immunology)
• Protein Sorting Signals (physiology)
• T-Lymphocytes, Cytotoxic (immunology, transplantation)