Stimulation of T cells by antigenic peptide complexed with isolated chains of major histocompatibility complex class II molecules.
Major histocompatibility complex (MHC) class II molecules are heterodimeric glycoproteins with one alpha and one beta polypeptide chain of similar molecular size. In this report, we describe the binding of an acetylated N-terminal peptide of myelin basic protein, [Ala4]MBP-(1-14), to purified individual alpha and beta chains of murine I-Ak molecules. Purified complexes of isolated single chains and antigenic peptide bind to cloned T cells restricted by I-Ak and [Ala4]MBP-(1-14) tetradecapeptide. The binding is blocked by alpha/beta anti-T-cell receptor (TCR) monoclonal antibody. Cell triggering as measured by an increase in extracellular acidification rate is observed when cloned T cells are exposed to purified complexes of isolated chains and antigenic peptide. This increase in the extracellular acidification rate is antigen specific and MHC-restricted, as chains alone or irrelevant chain-peptide complexes do not trigger an increase in the metabolic acidification rate. These results together demonstrate that in vitro cloned T cells are triggered by complexes of specific antigenic peptides and isolated individual chains of their cognate MHC proteins.
Nag
B
B
Anergen Incorporated, Redwood City, CA 94063.
Wada
H G
HG
Deshpande
S V
SV
Passmore
D
D
Kendrick
T
T
Sharma
S D
SD
Clark
B R
BR
McConnell
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000302:isolation & purification; D007700:Kinetics; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D008970:Molecular Weight; D004676:Myelin Basic Protein / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D004676:Myelin Basic Protein; D010446:Peptide Fragments