Structural and functional implications of a restricted antibody response to a defined antigenic region on the influenza virus hemagglutinin.
A group of hybridoma antibodies that recognize structurally overlapping epitopes on the influenza virus hemagglutinin have been analyzed for the sequence of their immunoglobulin heavy and light chain variable regions. All VH regions derive from the same gene family, and only two Vk genes, from different families, are involved. The repetitive and restricted use of these variable region genes indicates that considerable structural requirements influence the generation of antibodies specific for this region of the hemagglutinin. The degree of amino acid variability which is permissive for interaction with this region suggests that two thirds of the possible replacement mutations may abolish either antibody function or specificity. Analysis of the somatic mutation which occurred in the individual antibodies indicates that the light chains acquired replacement mutations at the rate predicted for random mutation. The heavy chains, however, accumulated a 3-fold excess of replacement mutations over that predicted for random accumulation, correlating with the dominant role they apparently play in determining fine differences in the specificity of these antibodies. The effect of somatic mutation on the clonal amplification and diversification of these B cell lineages is discussed.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics; D000917:Antibody Formation; D005796:Genes; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000302:isolation & purification; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000302:isolation & purification; D007075:Immunoglobulin M / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics
D000911:Antibodies, Monoclonal; D006389:Hemagglutinins, Viral; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D012333:RNA, Messenger; D012313:RNA