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 α and one β 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 α and β chains of murine I-Akmolecules. Purified complexes of isolated single chains and antigenic peptide bind to cloned T cells restricted by I-Akand [Ala4]MBP-(1-14) tetradecapeptide. The binding is blocked by α/β 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.