Human Leukocyte Antigens (HLAs) are glycoproteins that exhibit unusually high genetic polymorphism as well as high polygenecity by forming a wide variety of gene families. HLAs generally display peptides derived from intracellular proteins to T cells, and furthermore, they interact with various immune cell surface receptors to control broad aspects of immune responses pleiotropically, resulting in the maintenance of homeostasis in our body. X-ray crystallography has remarkably contributed to understanding of precise mechanisms for these HLA interactions. In this issue, we describe molecular structures of HLAs and HLA-receptor complexes, showing how HLA molecules regulate immune responses, and further discuss about their relationship with diseases.

A fluorescent microbeads assay with the Luminex system, used for detection of HLA antibody (Ab), is simple and highly sensitive. However, this method is indicated to detect clinically insignificant Abs such as low-titer HLA Abs and non-HLA Abs. While the IgG subclass and complement activation are reported to affect the transplantation outcomes, the relationship of HLA Ab and platelet transfusion refractoriness (PTR) is not fully understood. In this brief review, I summarize the evaluation of clinical significance of HLA Ab in PTR using in vitro phagocytosis assay of platelets with a pH sensitive dye.

Hematopoietic stem cell transplantation (HSCT) cures various hematologic diseases such as leukemia. History of development of HSCT could be categorized as “age of dawning” in 1970’s, “age of expansion” in 1990’s, when various transplant procedures were developed and indication of HSCT was expanded by the use of alternative sources of hematopoietic stem cells, establishment of bone marrow and cord blood banking, and the current “age of maturation”, when HLA barrier is breaking and quality of life posttransplant is improved. During such a long history of refinement of HSCT, long-term assumption of the requirements for successful HSCT, including HLA matching between the donor and host, myeloablative conditioning regimen, posttransplant immunosuppression, and germ-free environment has been revisited. In this issue, current status and future perspective of HSCT is discussed.

HLA is a major histocompatibility complex in human. HLA was discovered at the mid-1900s and recognized as an important element of immune response reaction. HLA contains the most polymorphic genes in humans. I will comment on polymorphisms in the HLA antigen and HLA genes.