Human Leukocyte Antigen Genotyping for Allogeneic Transplantations

The genetic diversity of human leukocyte antigen (HLA) molecules at the human population level enables the presentation of a broad spectrum of pathogen-derived peptides to T-cell receptors to launch adaptive immunity. However, the extreme polymorphism of HLA molecules results in HLA mismatches between most random donor-recipient pairs, which poses a significant immunologic barrier to allogeneic transplantations. This chapter provides background information on the process and clinical application of HLA typing, discusses the principle and challenges of HLA typing, and describes major molecular HLA typing methods, with a focus on next-generation sequencing. The transition from HLA phenotyping to genotyping by molecular-based methods was decisive and transformative. Hematopoietic stem cell transplantation is a life-saving treatment for selected hematopoietic malignancies and nonmalignant diseases. Solid organ transplant candidates may produce anti-HLA antibodies due to sensitization through previous blood transfusion, pregnancy, or transplantations.