Fine specificity and sequence of antibodies directed against the ectodomain of matrix protein 2 of influenza A virus

• Published in: Molecular Immunology 2006-07, Vol.43 (14), p.2195-2206
• Main Authors: Zhang, Manxin, Zharikova, Darya, Mozdzanowska, Krystyna, Otvos, Laszlo, Gerhard, Walter
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibodies, Viral - chemistry; Antibodies, Viral - immunology; Antibody; Antibody Specificity; Antigens, Viral - immunology; Antigens, Viral - metabolism; Base Sequence; Binding, Competitive; Complementarity Determining Regions; Genes, Immunoglobulin; Hybridomas; Immunoglobulin Heavy Chains - chemistry; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Light Chains - chemistry; Immunoglobulin Light Chains - genetics; Immunoglobulin Variable Region - chemistry; Immunoglobulin Variable Region - genetics; Influenza; Influenza A virus; Influenza A virus - immunology; Matrix protein 2; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Repertoire; Somatic Hypermutation, Immunoglobulin; Viral Matrix Proteins - immunology; Viral Matrix Proteins - metabolism
• ISSN: 0161-5890; 1872-9142; 1365-2567
• DOI: 10.1016/j.molimm.2005.12.015

The ectodomain of matrix protein 2 (M2e) has remained remarkably conserved amongst human influenza A viruses and is a target for Abs with protective activity. For these reasons, M2e is being investigated for its potential as a broadly protective influenza A virus vaccine. Here, we report on the fine specificity and sequence of seven M2e-specific mAbs isolated from three BALB/c mice after different immunization protocols. The mAbs recognized epitopes comprised within a 13 aa long peptide corresponding to M2e(4-16). They originated from 4 distinct precursor B cells and showed a highly restricted variable (V) gene usage, in that their heavy chain V regions were all formed by the same V H, D and J H gene segments and their light chain V regions made use of only two distinct Vκ genes (Vκ19-15 /IGKV6-15 and Vκ8-30 /IGKV8-30; NCBI/IMGT annotation, respectively). The consensus sequence of the expressed V H genes belongs to the J558 /HV1 family. It showed 96% identity with the BALB/c germline gene J558.n/IGHV1S137 and 100% identity with a V H gene expressed by several BALB/c B-1 B cells. This suggests that the consensus sequence is that of a functional BALB/c germline V H gene. The genetic restriction of this response may in part underlie the generally poor M2e-specific Ab response induced by infection.