Ac. Patera et al., IMMUNODOMINANCE WITH PROGENITOR B-CELL DIVERSITY IN THE NEUTRALIZING ANTIBODY REPERTOIRE TO INFLUENZA INFECTION, European Journal of Immunology, 25(7), 1995, pp. 1803-1809
We report striking immunodominance in the neutralizing antibody respon
ses of major histocompatibility complex congenic mice to natural infec
tion with influenza virus (H3N2 subtype), as deduced by sequencing the
hemagglutinin (HA) genes of monoclonal antibody (mAb)-selected mutant
viruses. A majority of mAb, established from individual BALB/c (H-2(d
)) mice, select mutant viruses containing the same single amino acid s
ubstitution in the membrane distal ectodomain, HA1 198 A-->E, whereas
changes at either HA1 158 G-->E or HA1 198 A-->E are selected for by m
Ab from BALB.K (H-2(k)) donors. The structural basis for immunodominan
ce, and potential diversity of progenitor B cells, was investigated by
sequence analysis of H and L chain gene rearrangements in mAb specifi
c for HA1 158 or HA1 198. No correlation was found between antibody sp
ecificity and V-H or V-L gene usage, and a minimum of three to six pro
genitor cells contributed to the individual's repertoire for a single
antigenic site. However, in a further analysis of the HA1 158-specific
antibody response of CBA/Ca (H-2(k)) donors, there was highly restric
ted light chain gene usage. Focusing of the immune repertoire to limit
ed regions of the HA molecule during a primary viral infection may be
a significant factor in immune pressure for antigenic variation, parti
cularly since there is no evident restriction in the antibody response
to immunization.