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

• Published in: Cell Vol. 89; no. 2; pp. 167 - 170
• Main Author: Bjorkman, Pamela J
• Format: Book Review Journal Article
• Language: English
• Published: United States Elsevier Inc 18.04.1997
• Subjects: Animals; Histocompatibility Antigens - chemistry; Ligands; Protein Conformation; Receptors, Antigen, T-Cell - chemistry
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80195-6

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. In the intervening 20 plus years, many pivotal discoveries have facilitated a molecular description of MHC-restricted T cell recognition: TCRs were found to resemble the antigen binding, or F sub(ab), portions of antibodies in sequence and domain organization; the form of antigen recognized by a TCR was discovered to be a peptide fragment bound to an MHC molecule; and crystal structures of MHC/peptide complexes revealed a surface composed of atoms derived from both the peptide and the MHC molecule. Taken together, these discoveries made the dual recognition requirements of TCRs (for the right antigen as well as the right MHC molecule) easier to understand, but direct visualization of a TCR binding its MHC/peptide ligand or even of a TCR alone eluded the efforts of many laboratories for years. This gap in our knowledge of TCR recognition has been filled by recent publications of crystallographic analyses of a TCR heterodimer and of TCRs binding to their MHC/peptide ligands.