BCR-ABL b2a2 fusion protein-derived peptide-HLA complex (BCR-ABL b2a2 pHLA)

The BCR-ABL b2a2-derived peptide-HLA complex is a tumor-specific neoantigen resulting from the reciprocal translocation t(9;22), which creates the Philadelphia chromosome (Bocchia et al., 1995, Blood). This translocation fuses exon 2 of the BCR gene with exon 2 of the ABL1 gene, generating a unique amino acid sequence at the b2a2 junction that is not found in the normal proteome (Rojas et al., 2007, Leukemia). These junctional peptides are processed and presented on the cell surface by HLA Class I and Class II molecules, where they can be recognized by the T-cell receptors (TCRs) of CD8+ and CD4+ T cells, respectively (Pinilla-Ibarz et al., 2000, Blood). This recognition triggers a targeted immune response against leukemic cells in patients with Chronic Myeloid Leukemia (CML) and Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL). Therapeutic interventions targeting this complex include peptide vaccines and TCR-engineered T-cell therapies (TCR-T), which aim to eliminate residual leukemic stem cells that persist despite treatment with tyrosine kinase inhibitors (Scheinberg et al., 2002, Leukemia). The specificity of the b2a2 junction makes it a promising candidate for precision immunotherapy with minimal off-target effects on healthy cells.

Other names

BCR-ABL b2a2 neoantigenb2a2 junctional peptidePhiladelphia chromosome-derived neoantigenBCR-ABL b2a2 pMHC complex

Selective recognition of the unique b2a2 fusion junction neoantigen by T-cell receptors to induce cytotoxic and helper T-cell responses against Philadelphia chromosome-positive leukemic cells.