INFLUENZA VIRUS HEMAGGLUTININ Original Antigenic Sin: A Bone Marrow-Derived Lymphocyte Memory Phenomenon Modulated by Thymus-Derived Lymphocytes

The "original antigenic sin" phenomenon (OAS) 1 challenges the dogma of the specificity of the immunological memory: when there is sequential infection with two different but antigenically related strains of influenza A virus, the antibody stimulated by the second infection reacts more strongly with the primary virus than with the one actually eliciting the response (1-3). This phenomenon is now well documented with many viral and nonviral cross-reacting antigens (4-8). However, its study with influenza antigens is of special interest because of its wide implications in the sero-epidemiology of influenza and the response to vaccination. In the accompanying paper (9) we have shown that purified hemagglutinin (HA) extracted from related influenza viruses share cross-reacting antigenic determinants, but differ in strain-specific determinants. We have now analyzed the antibody response to each of these groups of determinants after sequential exposure of mice to two related HA's, and have carried out cell-transfer experiments in an at tempt to elucidate the cellular mechanisms responsible for the aberrant immunological recall of the OAS phenomenon.