Major histocompatibility complex, class II, DR (HLA-DR) receptor (HLA-DR)

Major histocompatibility complex, class II, DR (HLA-DR) is a heterodimeric cell surface receptor consisting of an alpha and a beta chain (UniProt: P01903, P01911). It functions primarily in the adaptive immune system by presenting processed antigenic peptides to CD4+ T-helper cells. While expressed on professional antigen-presenting cells like B cells and dendritic cells, HLA-DR is also significantly upregulated on various hematologic malignancies. In the context of leukemia, HLA-DR on autologous leukemic cells serves as a specific target for monoclonal antibody therapies (PMID: 11560776). These therapeutic antibodies, such as apolizumab and IMMU-114, bind to the receptor to induce cell death through mechanisms like antibody-dependent cellular cytotoxicity and direct apoptosis (PMID: 21633038). Targeting HLA-DR allows for the selective elimination of leukemic blasts, although it also affects normal HLA-DR-positive immune cells. Clinical studies have demonstrated the efficacy of this approach in reducing tumor burden in patients with relapsed or refractory leukemia (PMID: 15150508). However, safety concerns such as B-cell depletion and myelosuppression must be managed during treatment. Monitoring the density of HLA-DR expression on malignant cells is a key biomarker for predicting therapeutic response. Overall, HLA-DR remains a critical target in the development of immunotherapies for blood-borne cancers.

Other names

Human leukocyte antigen – DR isotypeMHC class II antigenHLA-DR antigenHLA-DRB1/HLA-DRA complexMHC class II HLA-DR on autologous leukemic cells

Monoclonal antibodies targeting HLA-DR induce cell death through antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct induction of apoptosis via intracellular signaling pathways (PMID: 12149211).