Endothelial expression of nonclassic HLA molecules: functions and potential implication in clinical transplantation

Abstract

Purpose of review This review highlights expression and functions of nonclassic HLA class I molecules, their expression by human endothelial cells, and mechanisms by which they may significantly affect alloimmune responses to organ transplantation. Recent findings In contrast with classic class I major histocompatibility complex molecules, nonclassic major histocompatibility complex class I molecules, such as class I-related chain A, HLA-G, and HLA-E, are defined by limited polymorphism and restricted patterns of cellular expression. Human vascular endothelial cells have been shown to express major histocompatibility complex class I-related chain A, HLA-E, and receptors for HLA-G (immunoglobulin-like transcripts 3 and 4). The possibility that nonclassic class I molecules, expressed on graft endothelial cells, actively control regulatory mechanisms, not only to impair the destructive immune response mediated by natural killer cells and allospecific cytotoxic T lymphocytes but also to trigger specific tolerance induction, is attractive but must be validated. Summary In addition to classic class I and II major histocompatibility complex molecules, graft endothelial cells express nonclassic class I major histocompatibility complex molecules and receptors. The roles that the tightly regulated expression of nonclassic class I major histocompatibility complex molecules play in innate and acquired allogeneic response must be elucidated.