HLA structure and function in hematopoietic-cell transplantation

The degree of HLA compatibility between a patient and donor has formed the basis of donor selection since the development of allogeneic hematopoietic cell transplantation over 50 years ago and has advanced understanding of the basic immunobiology of HLA. New evidence supports a role for germline variation in the patient and the donor that do not require HLA matching for their effects to have clinical consequences. The discovery of novel non-coding polymorphisms, structural features of HLA molecules, and expression provide new models for donor selection and inspire the development of tools for clinical translation. Pairwise effects of HLA ligand/donor NK receptors may play an important role in transplant outcomes and showcase the value of understanding the role played by each constituent of the NK pathway in modulating donor responses to target antigens.