ITGB2-derived neoantigen presented on MHC molecules (ITGB2-neoantigen-MHC)

The ITGB2-derived neoantigen presented on MHC molecules is a class of immunogenic targets used in cancer immunotherapy, particularly for hematologic malignancies and certain solid tumors [1, 31]. The most prominent example is LB-ITGB2-1, a minor histocompatibility antigen (MiHA) derived from a splice variant of the ITGB2 (Integrin subunit beta 2, or CD18) gene [1, 19]. This specific peptide (GQAGFFPSPF) is presented by the MHC class I molecule HLA-B*15:01 and is associated with the single nucleotide polymorphism (SNP) rs760462 [21, 23]. Because ITGB2 expression is largely restricted to the hematopoietic lineage, these antigens are primarily found on leukemic cells in diseases such as Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML) [1, 19]. Therapeutic strategies targeting this complex include the use of TCR-engineered T cells and donor lymphocyte infusions (DLI) to induce a graft-versus-leukemia (GVL) effect [1, 25]. Additionally, somatic mutations in ITGB2 have been identified as potential neoantigen sources in solid tumors like glioma, where they correlate with tumor progression and immune evasion [26, 31]. Targeting these peptide-MHC complexes allows for highly specific immune-mediated destruction of malignant cells while minimizing damage to non-hematopoietic healthy tissues [1, 4].

Other names

LB-ITGB2-1ITGB2-derived minor histocompatibility antigenCD18-derived neoantigenrs760462-derived antigenITGB2-pMHC complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) triggers cytotoxic T-lymphocyte (CTL) activation, leading to the selective lysis of cells presenting the antigen.