Human leukocyte antigen – DR isotype and T-cell costimulatory molecules (HLA-DR/Costimulators)

HLA-DR is a Major Histocompatibility Complex (MHC) class II cell surface receptor that plays a critical role in the adaptive immune system by presenting processed antigenic peptides to CD4+ T-helper cells (UniProt P01903). T-cell costimulatory molecules, including members of the B7 (CD80/CD86) and CD28 families, provide the necessary secondary signals that determine the fate of a T-cell after it encounters an antigen (StatPearls, Physiology, Antigen Presenting Cells). Without these costimulatory signals, T-cells may become anergic or undergo apoptosis, whereas excessive signaling can lead to chronic inflammation or autoimmunity (PubMed: 29713477). In oncology, many costimulatory pathways are targeted by checkpoint inhibitors to restore the immune system's ability to recognize and destroy malignant cells (NIH, Immune Checkpoint Inhibitors). Conversely, in rheumatology and transplantation, these pathways are inhibited by drugs like Abatacept to prevent unwanted immune attacks on self-tissues or grafts (FDA Label, Orencia). Consequently, this group of molecules represents a cornerstone of modern immunotherapy across multiple therapeutic areas.

Other names

MHC class IIHLA-DRT-cell costimulatory receptorsImmune checkpointsCD28 familyB7 family

Modulation of T-cell activation through the inhibition or stimulation of secondary signaling pathways and antigen presentation (PubMed: 11244038, 21499297).