STIMULATION OF T-CELLS BY ANTIGEN-PRESENTING CELLS IS KINETICALLY CONTROLLED BY ANTIGENIC PEPTIDE BINDING TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES

Activation of CD4(+) T cells by antigenic peptide involves the interac tion of major histocompatibility complex (MHC) class II-peptide comple xes on the surface of antigen-presenting cells (APCs) with T-cell rece ptors. This report describes the kinetics of T-cell triggering by exog enous antigenic peptides in the presence of APCs. A rapid specific inc rease in extracellular acidification rate is observed within minutes u pon exposure of A.E7 T cells (restricted for IE(k) and moth cytochrome c peptide containing residues 88-103) and 4R3.9 T cells {restricted f or IA(k) and myelin basic protein peptide containing residues 1-14 [Ac MBP-(1-14)]} to their cognate peptides in the presence of CH27 cells b earing both IA(k) and IE(k) MHC class II molecules. Pretreatment of cl oned T cells, but not APCs, with herbimycin A resulted in complete inh ibition of triggering events, indicating that the acidification respon se is mediated by T-cell second messenger pathways. This rapid assay f or 4R3.9 T-cell stimulation showed increased T-cell triggering activit y for AcMBP-(1-14)-A(4) and MBP-(1-14)-M(4) peptides compared to the n ative AcMBP-(1-14)-K-4. By using the previously determined kinetic con stants for MBP-(1-14)-A(4) reactions with IA(k), it is possible to sho w that at the lowest peptide concentrations the kinetics of T-cell tri ggering are limited by the kinetics of the peptide binding to MHC clas s II molecules.