Human Major Histocompatibility Complex class II (MHC II) (HLA-II)

Human Major Histocompatibility Complex class II (MHC II) molecules are essential cell-surface glycoproteins primarily expressed on professional antigen-presenting cells, such as dendritic cells, B cells, and macrophages. Their primary biological role is to present exogenous peptides, derived from extracellular pathogens or proteins, to CD4+ T helper cells, thereby initiating and coordinating the adaptive immune response (StatPearls, 2023). In humans, these molecules are encoded by the Human Leukocyte Antigen (HLA) system, specifically the HLA-DR, HLA-DQ, and HLA-DP loci (NCBI, 2022). MHC II molecules play a pivotal role in maintaining self-tolerance; however, specific HLA-II alleles are strongly linked to the susceptibility of numerous autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, and celiac disease (Nature Reviews Immunology, 2021). In these conditions, MHC II molecules mistakenly present self-peptides to autoreactive T cells, leading to tissue damage. Therapeutic strategies targeting MHC II include the use of peptide mimetics to block the peptide-binding groove or monoclonal antibodies to modulate T-cell activation. For example, glatiramer acetate is a drug that competes with myelin-derived peptides for MHC II binding, effectively treating multiple sclerosis by shifting the immune response (PubMed, 2020).

Other names

MHC class IIHuman Leukocyte Antigen class IIHLA-DRHLA-DQHLA-DPMHC-II

Competitive inhibition of peptide binding to the MHC-II groove, modulation of T-cell receptor (TCR) signaling, and induction of immune tolerance.