Histocompatibility

Immune-mediated rejection of tissue allografts was first described in 1945 by the British immunologist Peter Medawar, followed by the discovery of the major histocompatibility complex (MHC) carrying the histocompatibility genes by Peter Gorer and George Snell in 1948, and of the human leukocyte antigen (HLA) molecules by Jean Dausset, Jon van Rood, and Rose Payne a decade later (Thorsby 2009). The importance of these discoveries was recognized by the Nobel Prices in Physiology and Medicine to Medawar, Snell, and Dausset in 1960 and 1980, respectively. Since then, the MHC has emerged as the single most polymorphic gene locus in eukaryotes, with 17,695 HLA alleles reported to date in the IMGT/HLA database, Release 3.31.0, 2018/01/19 (Robinson et al. 2015). While the main barrier to successful tissue grafting remain the HLA incompatibilities, also non-HLA polymorphisms have been recognized as important players, in particular minor histocompatibility antigens (mHAg), killer immunoglobulin-like receptors (KIR), and other polymorphic gene systems (Dickinson and Holler ; Gam et al. ; Heidenreich and Kröger ; Spierings 2014).