Complex between T-cell receptor, viral peptide and HLA-A2
Homo sapiens (human)
T-cells are lymphocytes derived from thymus and related to the immune response. They recognize antigens through the interaction of the T-cell receptor (TCR) expressed on the T-cell surface, and the complex of an antigen peptide and the class I or II major histocompatibility complex (MHC) molecule. The antigen specificity of each T-cell is determined according to the antigen recognition by TCR. Individual T-cells recognize only one type of antigen. Therefore many variants of T-cells exist, each of which expresses a TCR with a structure slightly different from the TCR of other T-cells, interacting with but one type of antigen. The antigen recognition by TCRs initiates signals in T cells that trigger development of the T-cell repertoire, regulation of the immune response and activation of cytolytic T cells. The previously determined structure of an antigen peptide bound to an MHC molecule has revealed that the peptide binds in a groove formed by two parallel alpha-helices located on the surface of MHC. Subsequently, the three-dimensional structure of human alpha-beta TCR complexed with the specific antigen, Tax peptide of the human T-cell lymphotropic virus HTLV-1, bound to the human MHC molecule HLA-A2, was determined.
The alpha-beta TCR consists of alpha and beta protein chains and is a major type of the TCR expression in T-cells. This receptor has variable loops, named CDR1, CDR2 and CDR3. The CDR1 and CDR3 loops in TCR are oriented diagonally over the Tax/MHC complex. All variable loops interact with Tax/MHC. In particular the CDR3 loops of both chains have many interactions with the Tax peptide. Over half of the peptide surface and MHC surface buried by TCR are covered by CDR3 loops, which are the most diverse in terms of the sequence of CDR loop in various TCR. It therefore has suggested that CDR3 loops are the major contributors to the repertoire selection. Thus, the mechanism of the antigen recognition by these variable loops has been revealed through this structure analysis. This orientation is similar to the one observed in mouse TCR/peptide/H-2K complex. Thus, in the TCR/antigen/MHC complex, the common binding feature is that CDR loops are oriented over antigen/MHC.
Protein Data Bank (PDB)
author: Yuko Tsuchiya