Tumor protein p53 R175H mutant peptide-HLA-A*02:01 complex (p53R175H-HLA-A*02:01)

The Tumor protein p53 R175H mutant peptide-HLA-A*02:01 complex consists of a mutant p53 peptide (HMTEVVRHC) bound to the HLA-A*02:01 molecule[1][2][3]. This complex forms when the p53 protein containing the R175H mutation (arginine at position 175 replaced with histidine) is processed into peptides that are presented on the cell surface by HLA-A*02:01[4]. The complex has been structurally characterized through crystallography, revealing that the p53R175H peptide occupies the binding cleft α1-α2 of HLA-A*02:01, burying a solvent-accessible surface area of approximately 870 Ų[2]. The C-terminal arginine at position 7 (Arg 174) and mutant histidine at position 8 (His 175) point upward out of the groove, while the N-terminus is situated deep within the peptide-binding cleft[2]. This complex is recognized by tumor-specific T cell receptors (TCRs) such as 12-6, 38-10, and 1a2, which have been isolated from patients with epithelial cancers[1]. These TCRs can discriminate between wild-type and mutant p53 epitopes with high specificity, making this complex an attractive target for cancer immunotherapy[1]. The p53R175H-HLA-A*02:01 complex can also be recognized by specific antibodies, such as H2-Fab, which has been crystallized in complex with the p53R175H/HLA-A*02:01[2][4]. This antibody recognition involves all six complementarity-determining regions (CDRs) making contact with the α1 and α2 helices of HLA-A*02:01[2]. The TP53 R175H mutation is one of the most common mutations in the TP53 gene, occurring in more than 50% of human cancers[7]. The resulting mutant p53 protein not only loses its normal tumor suppressor function but often acquires novel oncogenic properties[7]. The presentation of the p53R175H peptide by HLA-A*02:01 creates a tumor-specific neoantigen that can be targeted by the immune system, making it a promising target for cancer immunotherapy.

Other names

p53 R175H/HLA-A*02:01 complexHuman HLA-A*02:01&B2M&P53 R175H (HMTEVVRHC) Monomerp53R175H-HLA-A2

Recognition by tumor-specific T cell receptors (TCRs) Targeting by specific antibodies Immune-mediated elimination of cancer cells