HLA-DRB1 Protein, Human (Myc, His-SUMO)

The HLA-DRB1 protein serves as the beta chain of the antigen-presenting major histocompatibility complex class II (MHCII) molecule, forming a complex with the alpha chain HLA-DRA. This complex plays a pivotal role in presenting antigenic peptides on professional antigen-presenting cells (APCs), guiding alpha-beta T cell receptor (TCR) recognition by HLA-DRB1-restricted CD4-positive T cells. The process facilitates antigen-specific T-helper effector functions, including both antibody-mediated immune responses and macrophage activation, leading to the elimination of infectious agents and transformed cells. The protein typically presents extracellular peptide antigens of 10 to 30 amino acids, originating from the proteolysis of endocytosed antigens in lysosomes. In the tumor microenvironment, HLA-DRB1 presents antigenic peptides primarily generated in tumor-resident APCs, potentially via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins. Additionally, it presents peptides derived from intracellular proteins trapped in autolysosomes after macroautophagy, a mechanism relevant for T cell selection in the thymus and central immune tolerance. The selection of immunodominant epitopes follows distinct processing modes for pathogen-derived antigenic peptides and autoantigens/self-peptides. The anchor residue at position 1 of the peptide N-terminus, typically a large hydrophobic residue, is crucial for a high-affinity interaction with MHCII molecules. Specific alleles, such as DRB1*01:01, display immunodominant epitopes derived from various pathogens, illustrating the protein's diverse role in immune responses and tolerance mechanisms.