gamma-delta T cell receptor in complex with MHC T22
Mus musculus (house mouse)
Our immune system protects us from many different harmful agents called pathogens (bacteria, viruses, parasites and fungi). In invertebrates, the immune system is simple, involving protective barriers, toxic molecules and phagocytic cells that destroy invading pathogens by ingesting them. In vertebrates, the immune response is of two major forms - innate immune response and the adaptive immune response. The innate immune response is similar to that in invertebrates. It is the response that is first triggered when an infection occurs and does not depend on whether the host was previously exposed to the infection. The adaptive immune response is a more sophisticated defense mechanism that is triggered by the innate immune response. It is specific to a particular pathogen and depends on the previous exposure of the host to the pathogen. The adaptive immune response is carried out by white blood cells called lymphocytes in two forms - antibody response carried out by lymphocytes called B cells, and cell-mediated response carried out by lymphocytes called T cells. B cells respond by secreting proteins, called antibodies, which bind to the antigen (foreign body or pathogen) to inactivate it and mark it for destruction and ingestion by phagocytic cells. T cells can respond either directly to the signal presented by an antigen by killing the infected cell or by generating a signal to activate the macrophages to destroy the pathogen that they have phagocytosed. T cells recognize antigens through the presence of T cell receptors (TCRs) that are expressed on their surface. TCRs consist of two different polypeptide chains that are linked by disulphide bonds. Alpha beta TCRs are composed of an alpha chain and a beta chain, while the gamma delta TCRs are made up of gamma and delta chains. The variation in antigen binding sites of these receptors is caused by the recombination of the variable (V), diversity (D) and joining (J) gene segments. Alpha beta TCRs can recognize any antigen or antigenic peptide bound to major histocompatibility complex (MHC) molecules. The ligands of gamma delta TCRs have so far been unknown.
The structure shown here is that of the G8 gamma delta TCR bound to its antigen. The antigen is an MHC-like protein, T22. T22 is recognized by G8 independent of the cellular antigen-processing machinery that generates antigenic peptides which are required for antigen recognition by alpha beta TCRs. The orientation of the binding of T22 to G8 is also very different from the binding of MHC molecules to alpha beta TCRs, indicating the difference between the two types of TCRs.
Protein Data Bank (PDB)
author: Ashwini Patil