Ligand-specific oligomerization of T-cell receptor molecules.
T cells initiate many immune responses through the interaction of their T-cell antigen receptors (TCR) with antigenic peptides bound to major histocompatibility complex (MHC) molecules. This interaction sends a biochemical signal into the T cell by a mechanism that is not clearly understood. We have used quasielastic light scattering (QELS) to show that, in the presence of MHC molecules bound to a full agonist peptide, TCR/peptide-MHC complexes oligomerize in solution to form supramolecular structures at concentrations near the dissociation constant of the binding reaction. The size of the oligomers is concentration dependent and is calculated to contain two to six ternary complexes for the concentrations tested here. This effect is specific as neither molecule forms oligomers by itself, nor were oligomers observed unless the correct peptide was bound to the MHC. These results provide direct evidence for models of T-cell signalling based on the specific assembly of multiple TCR/peptide-MHC complexes in which the degree of assembly determines the extent and qualitative nature of the transduced signal. They may also explain how T cells maintain sensitivity to antigens present in only low abundance on the antigen-presenting cell.
Reich
Z
Z
Howard Hughes Medical Institute, School of Medicine, Stanford University, California 94305-5402, USA.
Boniface
J J
JJ
Lyons
D S
DS
Borochov
N
N
Wachtel
E J
EJ
Davis
M M
MM
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003574:Cytochrome c Group / Q000737:chemistry / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology; D007700:Kinetics; D008024:Ligands; D008027:Light; D051379:Mice; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology; D012542:Scattering, Radiation
D003574:Cytochrome c Group; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D011948:Receptors, Antigen, T-Cell