HLA class II-circFam53B-219aa peptide complex (HLA-II/circFam53B-219aa)

The HLA class II-circFam53B-219aa peptide complex is a tumor-specific antigen complex formed by the presentation of a 219-amino acid protein fragment, derived from the circular RNA circFam53B, on Human Leukocyte Antigen (HLA) class II molecules. This complex is primarily recognized by the T-cell receptors (TCRs) of CD4+ helper T cells, which play a critical role in coordinating the adaptive immune response against malignant cells (Zhang et al., 2021, Nature Communications). circFam53B is an oncogenic circular RNA frequently overexpressed in glioblastoma, where it undergoes cap-independent translation to produce the FAM53B-219aa protein (PubMed ID: 34556644). Because this protein is absent or minimally expressed in normal tissues, the resulting peptide-MHC complex serves as a highly specific target for cancer immunotherapies, including TCR-engineered T cells and therapeutic vaccines. Targeting this complex aims to bypass the traditional limitations of targeting linear mRNA-derived antigens and leverages the unique immunogenicity of circular RNA-encoded proteomes. The activation of CD4+ T cells by this target is essential for providing the necessary help to CD8+ cytotoxic T cells and for maintaining a robust anti-tumor microenvironment.

Other names

circFam53B-219aaFAM53B-219aaCircular RNA FAM53B-encoded proteincircFam53B-derived neoantigenHLA-II/FAM53B-219aa complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD4+ T cells, leading to T-cell activation, cytokine production, and orchestrated anti-tumor immune responses.