HLA-A*0201-restricted Receptor for Hyaluronan-Mediated Motility (RHAMM) R3 peptide-MHC complex (HLA-A2/RHAMM-R3)

The HLA-A2-bound RHAMM R3 epitope is a specific peptide-MHC complex consisting of the R3 peptide (sequence: ILSLELMKL) derived from the Receptor for Hyaluronan-Mediated Motility (RHAMM, also known as CD168 or HMMR) presented by the Human Leukocyte Antigen A*0201 (HLA-A*0201) molecule (Greiner et al., 2005). RHAMM is a tumor-associated antigen that is highly overexpressed in various hematological malignancies, such as acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and multiple myeloma, while maintaining restricted expression in most healthy tissues (Schmitt et al., 2008). This epitope serves as a critical therapeutic target for cancer immunotherapies, including peptide-based vaccines and T-cell receptor (TCR) engineered T-cell therapies. When presented on the surface of tumor cells or antigen-presenting cells, the R3 epitope is recognized by specific CD8+ cytotoxic T lymphocytes (CTLs), which then proliferate and execute targeted lysis of the RHAMM-expressing malignant cells (Giannopoulos et al., 2006). Clinical trials have demonstrated that vaccination with the R3 peptide can induce robust immune responses and clinical improvements in patients with myeloid leukemias (Schmitt et al., 2008). The target is particularly attractive because RHAMM expression correlates with disease progression and poor prognosis in several cancers, making it a relevant biomarker for patient selection and therapeutic monitoring (Tzankov et al., 2004).

Other names

CD168 R3 epitopeHMMR R3 peptideILSLELMKL-HLA-A*0201 complexRHAMM-R3HLA-A2-bound RHAMM R3 epitopeReceptor for Hyaluronan-Mediated Motility R3 epitope

Activation of CD8+ cytotoxic T lymphocytes (CTLs) that specifically recognize the R3 peptide (ILSLELMKL) presented by HLA-A*0201 on the surface of malignant cells, leading to targeted tumor cell lysis and immune-mediated clearance.