IMPROVED SENSITIZATION OF ANTIGEN-PRESENTING CELLS WITH TRANSFERRIN-BOUND PEPTIDES - ADVANTAGES IN COMPETITION FOR ANTIGEN PRESENTATION

T cells recognize peptides in association with major histocompatibilit y complex (MHC) molecules on the surface of antigen-presenting cells ( APC). To sensitize APC for antigen presentation in vitro and in vivo, high concentrations of synthetic peptides can be added from the outsid e and bind to the MHC molecules, thereby mimicking naturally processed peptides. In this report we investigated whether the transferrin (Tf) molecule could be used as a carrier to introduce antigenic peptides i nto the antigen presentation pathway of APC. We coupled to Tf various MHC class II DR1 restricted peptides and compared the sensitization of DR1(+) APC by the Tf-bound or by the soluble peptide, using peptide-s pecific T cell clones (TCC). The presentation of the Tf-bound peptides was MHC restricted and could be blocked by the fixation of the APC wi th glutaraldehyde or by the addition of an excess of Tf. Tf-bound pept ides were more efficiently presented than soluble peptides, since smal ler concentrations were required to sensitize APC. Moreover, they coul d compete with a soluble peptide for MHC restricted presentation with a very high efficiency if compared to soluble competing peptides. Tf p eptide conjugates could even compete with the presentation of a native antigen like tetanus toroid. Peptides bound to the transferrin molecu le might be useful for immunization strategies, as the relevant bound peptides are efficiently presented to peptide-specific TCC. (C) 1994 A cademic Press, Inc.