Purinergic receptor P2X 5 (P2RX5) peptide–HLA-A*03:01 complex (BRA#4–HLA complex)

The BRA#4 peptide–HLA complex is a minor histocompatibility antigen (mHAg) target composed of a polymorphic peptide derived from the purinergic receptor P2X 5 (P2RX5) presented by the HLA-A*03:01 molecule (de Rijke et al., 2005). This complex is generated due to a specific frameshift polymorphism (SNP rs1042856) in the P2RX5 gene, which creates a novel open reading frame in individuals carrying the allele (Overes et al., 2008). Because P2RX5 expression is highly restricted to hematopoietic cells—specifically B-cell lineage cells and certain myeloid cells—the BRA#4 complex serves as a promising target for immunotherapy in hematological malignancies (Griffioen et al., 2008). In the context of allogeneic hematopoietic stem cell transplantation (allo-SCT), targeting this complex allows for a selective graft-versus-leukemia (GvL) effect while minimizing the risk of graft-versus-host disease (GvHD) in non-hematopoietic tissues (Riddell et al., 2002). Therapeutic interventions currently under investigation include the use of donor-derived cytotoxic T lymphocytes (CTLs) and T-cell receptor (TCR) engineered T cells designed to recognize the BRA#4–HLA-A*03:01 complex (van Loenen et al., 2011).

Other names

Minor histocompatibility antigen BRA#4P2RX5-derived peptide–HLA complexBRA4 antigenB-cell restricted antigen 4

T-cell receptor-mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and targeted lysis of P2RX5-expressing cells.