CLONED T-CELLS INTERNALIZE PEPTIDE FROM BOUND COMPLEXES OF PEPTIDE AND PURIFIED CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGEN

Antigen presentation to helper T cells involves the formation of a tri molecular complex consisting of a class II major histocompatibility co mplex (MHC) antigen combined with an antigenic peptide on the surface of an antigen-presenting cell and a T cell receptor (TCR) on the T cel l. The fate of the MHC class II, peptide, or TCR moieties of the terna ry complex following antigen presentation is unknown. Using radio-labe led complexes of affinity-purified murine MHC class II molecules and p eptides corresponding to T cell epitopes of myelin basic protein (MBP) , this report presents evidence that the binding of preformed relevant MHC class II-peptide complexes to cloned T cells in vitro results in internalization of the peptide moiety. Neither the restricting MHC cla ss II molecule nor the TCR moiety of the trimolecular complex was inte rnalized by T cells. The specificity of peptide internalization was de monstrated using complexes of syngeneic MHC class II with an irrelevan t MBP peptide analog and by cloned T cells restricted for a different epitope of the same MBP antigen. Furthermore, the peptide translocatio n mediated by MHC class II and TCR was demonstrated by antibody-blocki ng experiments using anti-class II and anti-TCR monoclonal antibodies. The peptide internalization by T cells was markedly reduced when bind ing was performed at 4-degrees-C as compared with 37-degrees-C. In add ition, a significant inhibition of peptide translocation was observed in the presence of a metabolic inhibitor (sodium azide) but not in the presence of cytochalasin B. These results together demonstrate that t he in vitro interaction of soluble MHC II-peptide complexes with clone d T cells is an active process associated with uptake of the antigenic peptide.