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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.

Original publication




Journal article


Nat Rev Immunol

Publication Date





325 - 339


Antigen Presentation, Autoimmune Diseases, Disease, Gene Expression Regulation, Genes, MHC Class I, Genes, MHC Class II, Genetic Association Studies, Genetic Variation, HLA Antigens, Humans, Immunogenetic Phenomena, Immunotherapy, Models, Immunological, Molecular Mimicry, Protein Binding, Protein Stability, Receptors, Antigen, T-Cell, T-Lymphocytes