Assembly, specific binding, and crystallization of a human TCR-alphabeta with an antigenic Tax peptide from human T lymphotropic virus type 1 and the class I MHC molecule HLA-A2.
T lymphocytes use TCR-alphabeta to bind and to recognize complexes of antigenic peptides bound to MHC proteins located at the surface of APCs. We have assembled and crystallized this intercellular complex of TCR/peptide/MHC from soluble human TCR-alphabeta and soluble peptide/HLA-A2 complexes. The soluble TCR-alphabeta binds specifically to its in vivo ligand, the complex of HLA-A2, and a peptide from the Tax protein of human T lymphotropic virus type 1. The soluble TCR also binds in vitro to an altered peptide ligand, which appears to be a partial agonist in T cell assays as determined by its ability to elicit different cytolytic and lymphokine secretion responses. Heterodimerization and the antigenic specificity of the TCR do not require its interchain disulfide bond, transmembrane segments, or glycosylations. Crystals of the TCR/peptide/HLA-A2 complex diffract x-rays, providing the means to study in atomic detail the mechanism of Ag-specific cell-cell recognition between T cells and target cells.
Garboczi
D N
DN
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Utz
U
U
Ghosh
P
P
Seth
A
A
Kim
J
J
VanTienhoven
E A
EA
Biddison
W E
WE
Wiley
D C
DC
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D016356:Gene Products, tax / Q000276:immunology / Q000648:ultrastructure*; D015789:HLA-A2 Antigen / Q000648:ultrastructure*; D015486:HTLV-I Antigens / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism / Q000648:ultrastructure*; D013329:Structure-Activity Relationship
D004220:Disulfides; D016356:Gene Products, tax; D015789:HLA-A2 Antigen; D015486:HTLV-I Antigens; D046911:Macromolecular Substances; D016693:Receptors, Antigen, T-Cell, alpha-beta