The discovery of MHC restriction

The chance discovery 20 years ago that virus-specific cytotoxic T lymphocytes recognized antigen together with major histocompatibility complex (MHC) class I glycoproteins was the key to understanding immune surveillance of self. The altered-self hypothesis that was developed to explain these findings provided a reasonable biological basis for alloreactivity, MHC polymorphism and immune response (Ir) gene effects. Here, Nobel Laureates Rolf Zinkernagel and Peter Doherty remember the story behind the discovery of MHC restriction*.