Michael Bevan: Setting up T cell selection

10.1084/jem.20411ftaF rom t he A rch ive < / do ch ea d> New s< /d oc topi In the 1970s, Michael Bevan showed that T cells only recognize antigens in cells that have the same type of major histocompatibility complex (MHC) molecule present in the thymus where the T cells mature. His work provided the first clues to how thymic self-MHC molecules select the cells that make up the mature T cell repertoire. Every mature T cell specifically recognizes a particular combination of self-MHC molecule bound to a foreign peptide antigen. However, newborn T cells do not start out with the ability to recognize these complexes. During development, T cells re arrange their T cell receptor (TCR) genes, thus generating a diverse repertoire that includes those that do not recognize self-MHC. Only those that bind to self-MHC survive in the thymus. Groping in the dark In the early 1970s, this picture of thymic selection was still being colored in. Immunologists were unaware that the antigens recognized by T cells were peptides bound to MHC molecules. And TCRs themselves would not be defined for another decade. Despite these handicaps, Rolf Zinkernagel and Peter Doherty laid out the Nobel Prize–winning rules of what is now known as self-MHC restriction in 1973. They showed that antiviral T cells from an immunized mouse only recognized infected cells from other mice that shared the same type of MHC genes (1). Two theories were proposed to account for these data. The dual recognition hypothesis predicted that the antiviral T cells bore two receptors—one for a self-MHC molecule, and the other for the viral antigen (2). But Zinkernagel and Doherty preferred their own altered-self hypothesis, which proposed that the T cells bore a single receptor that recognized an MHC molecule that had been somehow altered by the viral infection. Altering a theory Michael Bevan, then a postdoctoral fello