Crystal Structure of the V _α Domain of a T Cell Antigen Receptor

Abstract

The crystal structure of the V alpha domain of a T cell antigen receptor (TCR) was determined at a resolution of 2.2 angstroms. This structure represents an immunoglobulin topology set different from those previously described. A switch in a polypeptide strand from one beta sheet to the other enables a pair of V alpha homodimers to pack together to form a tetramer, such that the homodimers are parallel to each other and all hypervariable loops face in one direction. On the basis of the observed mode of V alpha association, a model of an (alpha beta)2 TCR tetramer can be positioned relative to the major histocompatibility complex class II (alpha beta)2 tetramer with the third hypervariable loop of V alpha over the amino-terminal portion of the antigenic peptide and the corresponding loop of V beta over its carboxyl-terminal residues. TCR dimerization that is mediated by the alpha chain may contribute to the coupling of antigen recognition to signal transduction during T cell activation.

A Human CTL Recognizes a Caspase-8-Derived Peptide on Autologous HLA-B*3503 Molecules and Two Unrelated Peptides on Allogeneic HLA-B*3501 Molecules

“…Thus, CTL 121 expresses only one TCR. Taking into account the conserved conformation of the CDR1␣ loops that have been studied so far by crystallography (30), the CDR1␣ amino acid sequence of the TCR of CTL 121 was compared with the sequence of TCR A6 interacting with a tax peptide presented by HLA-A2. The crystal structure of this last TCR had revealed that it was the Q at position 30 of the CDR1␣ that interacts with a neutral G at position 4 of the peptide (31).…”

Differential Roles of T Cell Receptor α and β Chains in Ligand Binding Among H-2Kd-restricted Cytolytic T Lymphocyte Clones Specific for a Photoreactive Plasmodium berghei Circumsporozoite Peptide Derivative

“…Conversely, crystallographical studies on a BV8S2A1 encoded TCR ␤ chain and an AV4S2 TCR ␣ chain fragment confirmed that TCR are folded in an Ig-like manner but also indicated significant structural differences, such as different hinge structures and interstrand hydrogen bond formation (4,5). Little is still known on how TCR bind their ligand (MHCpeptide complexes).…”

T‐Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4+ and CD8+ T‐Cell Subsets

“…Three complementarity-determining regions (CDR1, CDR2 and CDR3) have been defined for each of the two TCR chains. Although challenged by some recent studies [3][4][5][6], the portion of the TCR essentially responsible for interaction with the antigenic peptide has been claimed to lie in the CDR3 loops of the two variable regions [1,[7][8][9][10][11][12]. By definition, part of the CDR3 region is encoded by a given J gene segment [7].…”