The major histocompatibility complex (MHC) is an evolutionary mechanism unique to vertebrates. In humans, the MHC is known as the human leukocyte antigen (HLA) system. In mice, the MHC is known as H2.
MHC was first studied in mice involving tumor tissue transplantation in the 1940s. Tumor tissue rejection rates were measured from tumor tissue transplants between strains of inbred mice compared to non-inbred strains. Inbred mice were more tolerant of the transplanted tissue compared to non-inbred mice.
Around the same time, concerned physicians were looking for reasons to explain unexplained transfusion reactions despite ABO compatibility and contemporary RBC antigen matching. Researchers at the time hypothesized leukocytes were behind the unexplained reactivity. HLA antibodies were discovered from multiple transfused blood products and multi-parous people. This led to the discovery of HLA class I and II glycoproteins that are evaluated by molecular and serological methods to date.
