Dimerization of soluble major histocompatibility complex-peptide complexes is sufficient for activation of T cell hybridoma and induction of unresponsiveness.
Major histocompatibility complex (MHC) class I molecules are cell-surface proteins that present peptides to CD8+ T cells. These peptides are mostly derived from endogenously synthesized protein. Recombinant, soluble MHC class I molecules were produced, purified, and loaded homogeneously with synthetic peptide. These MHC-peptide complexes were used to activate a T cell hybridoma. While monomers of MHC-peptide bound to the T cell, they showed no stimulatory activity. Dimers fully triggered the T cell hybridoma to secrete interleukin 2. This response was followed by a state in which the T cell was refractory to restimulation as a result of defective signal transduction through the T cell receptor.
Abastado
J P
JP
Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Medicale U277, Paris, France.
Lone
Y C
YC
Casrouge
A
A
Boulot
G
G
Kourilsky
P
P
D000595:Amino Acid Sequence; D000818:Animals; D006183:H-2 Antigens / Q000737:chemistry* / Q000276:immunology; D006825:Hybridomas; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D012995:Solubility; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
D006183:H-2 Antigens; D046911:Macromolecular Substances; D010455:Peptides; D011948:Receptors, Antigen, T-Cell