Modulation of Tumor Immunity by Soluble and Membrane-Bound Molecules at the Immunological Synapse

Figure 1

The structure of the T cell receptor (TCR) and its ligand, the peptide-MHC complex (pMHC). The TCR is a disulfide-bound heterodimer composed by one alpha (dark green) and one beta (blue) chain. Diversity within TCR molecules is mainly concentrated at the complementarity determining regions (CDRs, in red and orange) of the alpha and beta chains at the antigen-recognition region. Antigenic peptides are presented in the peptide groove of MHC molecules. MHC-I molecules are composed by an alpha chain (pink) that harbors the peptide-presentation groove and a small beta-2 microglobulin chain (yellow, 𝛽₂ m). On the other hand, MHC-II molecules are composed by one alpha (pink) and one beta (yellow) chain. As shown for this molecule, the peptide-presentation groove in these molecules is formed by both chains. Antigenic peptides (green) have amino acids that are exposed to the TCR molecule and amino acids that are buried within the MHC groove. Left: the TCR/pMHC complex of a human melanoma-specific TCR (DMF5) bound to MHC-I HLA-A2 with the the MART-1 (26–35) peptide (RCSB Protein Data Bank accession number DOI: 10.2210/pdb3qdg/pdb, 3QDG). Right: the TCR/pMHC complex of a human melanoma-specific TCR (E8) bound to the MHC-II molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase (RCSB Protein Data Bank accession number DOI: 10.2210/pdb4e41/pdb, 4E41). Both molecules were modeled using the software ViewerLite 5.0 from Accelrys Inc.