Quaternary structure of a carrier protein influences antigenicity and immunogenicity of an inserted T cell determinant.
To study the influence of the quaternary structure of the outer membrane protein PhoE of Escherichia coli on the presentation of an inserted T cell epitope, an epitope comprising amino acid residues 72-85 of myelin basic protein (MBP) was inserted at different sites in PhoE. This sequence is the critical T cell epitope in experimental autoimmune encephalomyelitis (EAE) in Lewis rats. The antigenicity and immunogenicity of two different conformational forms of the chimeric PhoE constructs, i.e. the denatured monomeric form and the native trimeric form, were studied. It appeared that the monomeric form, but not the native trimeric form of such PhoE constructs induced proliferation of the MBP72-85-specific T cell line Z1a. This conformational discrepancy was independent of the site in PhoE in which the epitope was inserted. Immunization with the monomeric form of PhoE constructs resulted in the priming of MBP72-85-specific T cells. In contrast, the trimeric form of these constructs was much less efficient in priming such cells. The differences between the monomeric and trimeric forms were most apparent when induction of EAE was studied. The monomeric form was encephalitogenic while the trimeric form was not. Furthermore, the antigen fine specificity, Vbeta usage and encephalitogenicity of T cells triggered by immunization with a monomeric PhoE construct appeared to be the same as those of T cell line Z1a, which was obtained after immunization with MBP, indicating that similar cells are triggered by immunization with the epitope either in PhoE or in its native context.
Janssen
R
R
Department of Molecular Cell Biology, Institute of Infectious Diseases, Utrecht University, Utrecht, The Netherlands.
Wauben
M H
MH
Tommassen
J
J
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001704:Biopolymers / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology; D029968:Escherichia coli Proteins; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D018272:Porins / Q000276:immunology; D011487:Protein Conformation; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship
D000485:Allergens; D000941:Antigens; D001704:Biopolymers; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein; D018272:Porins; C082922:PhoE protein, E coli