Rho GTPase-activating protein 45 (Minor histocompatibility protein HA-1) (HA-1)

Rho GTPase-activating protein 45 (ARHGAP45), commonly known as Minor histocompatibility protein HA-1, is a hematopoietic-restricted protein that acts as a Rho GTPase-activating protein (RhoGAP), regulating actin cytoskeleton remodeling and cell spreading [2, 6, 9]. It is widely recognized as a key minor histocompatibility antigen (mHAg) due to a single nucleotide polymorphism (rs1801284) that creates an immunogenic nonamer peptide (HA-1H) presented by HLA-A*02:01 [5, 10, 11]. Because its expression is predominantly limited to cells of the hematopoietic lineage, it is a highly attractive target for immunotherapy in allogeneic hematopoietic stem cell transplantation (HSCT) [8, 10, 20]. Therapeutic approaches, such as HA-1 peptide vaccines and TCR-engineered T-cell therapies, aim to induce a 'Graft-versus-leukemia' (GvL) effect to eliminate residual cancer cells while avoiding systemic 'Graft-versus-host disease' (GvHD) in other organs [10, 18, 20]. Although primarily hematopoietic, aberrant expression has been reported in some solid tumors like melanoma, potentially expanding its utility as a therapeutic target [15, 17]. Monitoring for HLA-A*02:01 status and HA-1 genotype disparity between donor and recipient is critical for patient selection and efficacy assessment [5, 10].

Other names

HMHA1ARHGAP45Minor histocompatibility antigen HA-1KIAA0223Rho GTPase-activating protein 45

Stimulation of donor-derived cytotoxic T-lymphocyte (CTL) responses against cells presenting the immunogenic HA-1 peptide in the context of HLA-A*02:01.