HLA class I-restricted BCR-ABL p210 (b2a2) junction peptide complex (HLA-BCR-ABL (b2a2))

The HLA class I-restricted BCR-ABL p210 (b2a2) junction peptide complex is a tumor-specific neoantigen target found on the surface of cells harboring the Philadelphia chromosome (t(9;22)). This translocation creates the BCR-ABL1 fusion gene, which produces a chimeric protein with a unique amino acid sequence at the fusion junction. In the p210 b2a2 isoform (also known as e13a2), exon 2 of BCR is joined to exon 2 of ABL, creating a neoepitope that is processed and presented by specific HLA class I alleles, such as HLA-A*02:01 or HLA-A*03:01 (Bocchia et al., 1996). Because this peptide sequence is entirely absent from the normal human proteome, the complex serves as a highly specific target for immunotherapy, minimizing the risk of off-tumor toxicity. Therapeutic strategies targeting this complex include peptide-based vaccines designed to elicit endogenous T-cell responses and adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize the pHLA complex (Pinilla-Ibarz et al., 2000). Clinical studies have demonstrated that vaccination with these junctional peptides can induce specific cytotoxic T-lymphocyte (CTL) responses in patients with chronic myeloid leukemia (CML) (Scheinberg et al., 2002). However, challenges remain, including the potential for immune evasion through HLA downregulation and the relatively low density of the target complex on the leukemic cell surface.

Other names

BCR-ABL b2a2 neoantigenp210 b2a2 junctional peptidee13a2 BCR-ABL fusion peptidePhiladelphia chromosome-derived neoantigenBCR-ABL1 fusion peptideBCR-ABL p210 b2a2 pHLA

Recognition of the specific peptide-HLA complex by T-cell receptors (TCRs) on cytotoxic T lymphocytes, leading to the targeted destruction of cells expressing the BCR-ABL fusion protein (Bocchia et al., 1996).