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

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 recoanized 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 V-K genes (V(K)19-15/IGKV6-15 and V(K)8-30/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/IGHVIS137 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. (c) 2006 Elsevier Ltd. All rights reserved.