The immune response of BALB/c mice to influenza hemagglutinin: commonality of the B cell and T cell repertoires and their relevance to antigenic drift

An extensive analysis of the class II (I-Ad)-restricted T cell repertoire for influenza hemagglutinin (HA) of the H3 subtype, elicited by natural infection, has shown that a majority of CD4 memory T cell clones focus on antibody-binding regions of HA, sites B and E, and are sensitive to the residue substitutions that have occurred in these regions during antigenic drift. The proliferative responses of CD4 clones to synthetic peptides have identified T cell epitopes within site B, HA1 177–199 and HA1 182–199, and site E, HA1 56–76. The recognition specificity of T cell clones for antibody-selected mutant viruses, with single amino acid substitutions within these recognition sites identified residues 63, 189, 193 and 198 as being important for T cell recognition and thus established that BALB/c, CD4 T cell clones were sensitive to the same substitutions known to abrogate BALB/c antibody recognition of the native HA. Our findings indicate extensive commonality of the B cell and T cell repertoires for HA, which may be relevant to an understanding of the immune pressures for antigenic drift, and, moreover, suggest that the antigen-specific B memory cell may be instrumental in selection of the peripheral T cell repertoire.