Physics

Pathology

Human leukocyte antigen

Disease

Biology

Antigen

Variation (astronomy)

Astrophysics

Genetics

Medicine

Nature reviews. Immunology

Technological advances have given valuable insight into the molecular mechanisms that underpin the association between HLA genetics and disease. Dendrou and colleagues review mechanisms of HLA–peptide–T cell receptor binding in health and disease and discuss how this knowledge may be translated into clinical benefit. Fifty years since the first description of an association between HLA and human disease, HLA molecules have proven to be central to physiology, protective immunity and deleterious, disease-causing autoimmune reactivity. Technological advances have enabled pivotal progress in the determination of the molecular mechanisms that underpin the association between HLA genetics and functional outcome. Here, we review our current understanding of HLA molecules as the fundamental platform for immune surveillance and responsiveness in health and disease. We evaluate the scope for personalized antigen-specific disease prevention, whereby harnessing HLA–ligand interactions for clinical benefit is becoming a realistic prospect.

HLA variation and disease