MHC Restriction in Three Dimensions: A View of T Cell Receptor/Ligand Interactions

Abstract

B and T lymphocytes of the immune system employ a highly effective diversity-generating machinery to ensure that their receptors, antibodies and T cell receptors (TCRs), respectively, have the capacity to recognize an enormous array of antigens. Indeed, antibodies can be raised against many kinds of molecules that are perceived as foreign to the host, including proteins, carbohydrates, small organic compounds, and nucleic acids. TCRs, on the other hand, have the seemingly peculiar property that they only recognize a foreign antigen when it is associated with a host- or “self”-encoded protein called a major histocompatibility complex (MHC) molecule. The T cell property of “MHC-restricted” recognition of antigen was discovered for cytotoxic T cells by Zinkernagel and Doherty 1974, work for which they received the 1996 Nobel Prize in Medicine.