Differential antigen presentation of hepatitis B surface antigen on cell membranes of responder and nonresponder mice.
In several systems it has been shown, that non-responsiveness to an antigen in mice of a particular haplotype is due to the lack of binding of an immunogenic peptide to class II molecules. Such studies have been done using detergent solubilized, affinity purified class II molecules. It has been reported, that the presence of certain phospholipids around class II molecules dramatically alters the extent of peptide binding to these molecules. It thus appears that the milieu in which the class II molecules are inserted influences to a considerable extent the level of peptide binding. Hence it is likely that the kinetics of binding of immunogenic peptides to class II on the cell surface, may be different from that of molecules inserted in detergent micelles. We therefore decided to test this by studying the binding of radiolabeled peptides to class II molecules on cell membranes. We report here a rapid and sensitive assay for peptide binding to murine class II molecules on cell membranes. Further, we have used this assay to study the nature of the interaction of immunogenic peptides and class II molecules on cell membranes of mice who are responders and non-responders to Hepatitis B surface Antigen (HBsAg). Interestingly, we find that immunogenic peptides bind in good correlation with their MHC restriction. We also observed that the HBsAg derived peptide which is unable to elicit a T cell response in the non-responder but fails to make a stable class II-peptide complex.(ABSTRACT TRUNCATED AT 250 WORDS)
Rajadhyaksha
M M
MM
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Thanavala
Y M
YM
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D000937:Antigen-Antibody Reactions / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology*; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000276:immunology; D013154:Spleen / Q000166:cytology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments