Non-MHC antigenic targets of the humoral immune response in transplantation

There is a growing body of data supporting a role for non-HLA antibodies in acute and chronic rejection of solid organ transplants. While many of these non-HLA antigens remain poorly defined, the principal antigenic targets are expressed on cells of the allograft including endothelium and epithelium. These non-HLA antigens are classified as either alloantigens, such as the major histocompatibility complex class I chain-related gene A (MICA) or MICB, or tissue-specific autoantigens such as vimentin, cardiac myosin (CM), collagen V (Col V), agrin, and angiotensin II receptor type I (AT1). Herein we provide an overview of the non-MHC antigenic targets that have been implicated in graft rejection and discuss the interplay between alloimmunity and autoreactivity in graft rejection.