Clonal repertoire diversification of a neutralizing cytomegalovirus glycoprotein B-specific antibody results in variants with diverse anti-viral properties.
Cytomegalovirus induces a chronic infection that in normal individuals is controlled by the immune system. In the case of humoral immunity, epitopes, in particular antigenic domain-1, in glycoprotein B have proven to be important for the induction of virus-neutralizing activity. Such antibodies can exert potent virus-neutralizing activity but can also block neutralizing antibodies from binding. Furthermore, these antibodies differ in their fine recognition of antigenic domain-1 as determined by epitope mapping. By using combinatorial library and phage display technologies we have now isolated a large array of clonally related antibody fragments to understand the origin of this diversity. This procedure allowed us to demonstrate that much of the diversity in functional activity (virus neutralization) and epitope recognition can arise from a single parental molecule through somatic mutation processes. We have thus demonstrated that the clonal diversification of a single antigen-specific clone can account for much of the diversity in antibody anti-viral activity. These findings have implications on the development of a gB-based subunit vaccine, as an effective vaccine preparation need not only to recruit appropriate clones into the immune response but also to evolve them properly so as to maintain an appropriate biological function.
Barrios
Yvelise
Y
Department of Immunotechnology, Lund University, BMC D13, S-22184 Lund, Sweden.
Knör
Susanne
S
Lantto
Johan
J
Mach
Michael
M
Ohlin
Mats
M
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000235:genetics / Q000494:pharmacology*; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003587:Cytomegalovirus / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D005347:Fibroblasts; D006801:Humans; D007128:Immunoglobulin Fragments / Q000494:pharmacology*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D007128:Immunoglobulin Fragments; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus