Human leukocyte antigen class II (HLA-II) (HLA-II)

Human leukocyte antigen class II (HLA-II) molecules are heterodimeric cell surface glycoproteins that play a fundamental role in the adaptive immune system by presenting exogenous peptides to CD4+ T helper cells (UniProt: P01903, P04229). Primarily expressed on professional antigen-presenting cells (APCs) such as dendritic cells, B cells, and macrophages, HLA-II molecules are critical for initiating and regulating immune responses (PMID: 30046154). In oncology, HLA-II expression can be induced on tumor cells by inflammatory cytokines like interferon-gamma, and specific peptide-HLA-II complexes serve as targets for novel immunotherapies, including TCR-engineered T cells and bispecific antibodies (PMID: 28636541). Furthermore, HLA-II acts as a ligand for the inhibitory checkpoint receptor LAG-3, making the HLA-II/LAG-3 axis a significant target for cancer immunotherapy, as exemplified by the FDA-approved drug Relatlimab (PMID: 32814723). Beyond cancer, HLA-II molecules are central to the pathogenesis of autoimmune diseases where they may present self-antigens, and they remain major determinants of histocompatibility in clinical transplantation (StatPearls: NBK541019). Therapeutic challenges include the risk of on-target, off-tumor toxicity due to the constitutive expression of HLA-II on healthy immune cells, which can lead to systemic immunosuppression or severe inflammatory reactions (PMID: 31434694).

Other names

MHC class IIMajor histocompatibility complex class IIHLA-DRHLA-DQHLA-DPHLA-DMHLA-DO

Modulation of the LAG-3/HLA-II immune checkpoint to enhance T-cell activity; direct targeting of tumor-specific peptide-HLA complexes via engineered T-cell receptors (TCR-T); induction of antibody-dependent cellular cytotoxicity (ADCC) against HLA-II-expressing malignant cells.