Immunodominance of a recombinant T-cell epitope depends on its molecular environment.
In the present study, we have investigated the influence of the molecular environment of a T-cell epitope on its immunogenicity. We genetically inserted into different sites of two bacterial recipient proteins, LamB or MalE, an immunodominant T-cell epitope: the 120-132 T-cell epitope from the PreS2 region of HBV. The T-cell epitope was introduced, either alone (PreS:T) or with an adjacent B-cell epitope (PreS:TB). After purification, the hybrid proteins were injected into mice and we studied the immunogenicity of recombinant T-cell epitopes by analyzing the in vitro proliferative responses of LN cells from these mice to the inserted peptides. The immunization of mice with recombinant MalE protein containing the PreS:T or PreS:TB peptides at two different sites induced strong peptide-specific proliferative responses, indicating that the insertion sites did not affect the immunodominance of the inserted T-cell epitope. A strong T-cell proliferative response was also obtained after immunization of mice with hybrid LamB protein containing the PreS:TB epitope at position 153. In contrast, the recombinant proteins which contained only the PreS:T epitope at positions 153 or 374 failed to stimulate T-cell responses. Therefore, this study demonstrates that the immunogenicity of recombinant T-cell epitopes may be strongly affected both by the insertion site and by inserted adjacent residues.
Leclerc
C
C
Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France.
Martineau
P
P
Charbit
A
A
Lo-Man
R
R
Dériaud
E
E
Hofnung
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins; D002213:Capsid / Q000235:genetics / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D058619:Maltose-Binding Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000235:genetics / Q000276:immunology; D018272:Porins; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D000956:Antigens, Viral; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D006514:Hepatitis B Surface Antigens; D016056:Immunodominant Epitopes; D058619:Maltose-Binding Proteins; D018272:Porins; D011498:Protein Precursors; D011991:Receptors, Virus; D011994:Recombinant Proteins; C016532:maltoporins; C050807:presurface protein 2, hepatitis B surface antigen