The effect of soluble and membrane-bound antibody on presentation of soluble antigen to helper T cells has been extensively studied. Factors that determine whether an antibody enhances or inhibits antigen presentation include epitope specificity and the nature of the surface receptors on the antigen presenting cell that mediate antigen uptake. Synthetic peptides composed of defined B and helper T cell epitopes offer a different approach to investigate antibody effects on antigen uptake and processing. Peptide antigen typically is characterized by a restricted number of epitopes, compared to a larger protein. Further, peptide, in contrast to protein antigen, may not have to be processed. The development of a model for studying presentation of a peptide antigen that does not require processing will allow the investigation of antibody effects in a different system than the whole-protein model so extensively studied. Antigen presentation to a T cell hybridoma clone can be studied in the presence and absence of peptide-binding monoclonal antibodies specifically targeted to areas of peptide with potentially different contributions to antigenicity. This project will establish a model for the investigation of antibody effects on the presentation of peptide antigen that does not require processing. A peptide-specific T cell hybridoma will be developed for use in investigating the effect of monoclonal antibodies targeted at residues that are critical for presentation with recognition of the peptide antigen as compared to residues that are not critical. This model will continue to be used to investigate other factors, such as receptor-mediated antigen uptake, that affect antibody influence on antigen uptake, processing, and presentation. The model established in this project will generate information specifically focused on antigen presentation that will be relevant in the context of the continuing evaluation of synthetic peptides as immunogens.
