EWS-FLI1 fusion protein type 2 junctional peptide presented by MHC class I (EWS-FLI1/MHC-I)

The EWS-FLI1 fusion protein type 2 junctional peptide presented by MHC class I is a highly specific tumor neoantigen complex associated with Ewing sarcoma. This complex arises from the t(11;22)(q24;q12) chromosomal translocation, specifically the Type 2 variant where EWS exon 7 is fused to FLI1 exon 5 (Meyer-Wentrup et al., 2005). The resulting fusion protein acts as an aberrant transcription factor driving oncogenesis, but the unique amino acid sequence at the fusion breakpoint also serves as a source of tumor-specific peptides (Evans et al., 2015). When these peptides, such as the EF-2 epitope, are processed and displayed by Major Histocompatibility Complex (MHC) Class I molecules (typically HLA-A*02:01), they become visible to the cellular immune system (Liu et al., 2020). This makes the complex a primary target for precision immunotherapies, including TCR-engineered T-cells and TCR-like antibodies, which aim to exploit the absolute absence of this sequence in normal human proteomes. However, therapeutic efficacy can be challenged by the relatively low density of these complexes on the cell surface and the potential for tumor escape through MHC downregulation (Bossiwala et al., 2023).

Other names

EWS/FLI-2 fusion protein EF-2 epitopeEWS-FLI1 type 2 neoantigenEWS-FLI1 breakpoint peptideEWS-FLI1 junctional epitopeHLA-A*02:01-restricted EWS-FLI1 peptide

Targeting of tumor cells via T-cell receptor (TCR) recognition of the specific junctional peptide-MHC complex, leading to directed T-cell mediated cytotoxicity and tumor cell lysis.