Redistribution of a murine humoral immune response following removal of an immunodominant B cell epitope from a recombinant fusion protein.
Immunization of different mice strains with a recombinant fusion protein composed of the vector-encoded N-terminal leader peptide CroLac (containing lambda Cro and LacI fragments) and a part of the transmembrane protein of HIV-1 (gp41) led to a high anti-CroLac humoral immune response. A detailed analysis of this response revealed the presence of an immunodominant, linear B cell epitope localized near the C-terminus of the CroLac fragment. The immune response seemed to be biased towards this epitope since few or no monoclonal antibodies (mAb) could be generated against the remaining part of CroLac and the gp41 fragment. Upon removal of the immunodominant region from the fusion protein the immune response was redirected and spread over the previously non-immunogenic regions. Consequently, we report a model system in which an immunodominant B cell epitope biases the immune response away from less immunogenic epitopes on the same molecule.
Scheerlinck
J P
JP
Institute of Molecular Biology, Vrije Universiteit Brussel, St-Genesius-Rode, Belgium.
DeLeys
R
R
Saman
E
E
Brys
L
L
Geldhof
A
A
De Baetselier
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000917:Antibody Formation; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D004268:DNA-Binding Proteins; D000939:Epitopes; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012097:Repressor Proteins / Q000276:immunology; D013329:Structure-Activity Relationship; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D001616:beta-Galactosidase / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; D001616:beta-Galactosidase