Heat shock protein 70-derived peptide-Human leukocyte antigen class I complex (HSP70-HLA-I)

The Heat shock protein 70-derived peptide-Human leukocyte antigen (HLA) class I complex is a molecular assembly presented on the surface of cells, particularly malignant ones, where it serves as a target for T-cell recognition. Heat shock protein 70 (HSP70) is a highly conserved molecular chaperone that is frequently overexpressed in various cancers, including lung, liver, and colon carcinomas, to facilitate protein folding and provide cytoprotection against environmental stressors [1][2]. Peptides derived from the intracellular processing of HSP70 are loaded onto HLA class I molecules and transported to the cell membrane. This peptide-MHC (pMHC) complex acts as a tumor-associated antigen (TAA) that can be specifically recognized by the T-cell receptors (TCRs) of cytotoxic T-lymphocytes [3]. Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies, such as TK-8001, and therapeutic peptide vaccines designed to stimulate an endogenous anti-tumor immune response [4][5]. The clinical utility of this target is often restricted by the requirement for specific HLA alleles, such as HLA-A*02:01, in the patient population [6]. Sources: [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369757/ [2] https://pubmed.ncbi.nlm.nih.gov/15155834/ [3] https://www.nature.com/articles/s41417-020-0173-z [4] https://www.takara-bio.co.jp/en/news/2019/03/11.html [5] https://clinicaltrials.gov/ct2/show/NCT03860233 [6] https://www.uniprot.org/uniprotkb/P0DMV8/entry

Other names

HSP70 peptide-MHC complexHSPA1A-HLA-A*02:01 complexHSP70-derived epitope-HLA class IHSP70-pMHCHeat shock protein 70-HLA-A2

Recognition by engineered or endogenous T-cell receptors (TCRs) leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of cells presenting the HSP70-derived peptide.