An analysis of the specificity and immunodominance of the T cell response to the hemagglutinin molecule of influenza virus

Ann Marie Haberman, University of Pennsylvania


The BALB/c T cell response to influenza virus A/PR/8/34 hemagglutinin (HA) has been used as a model system for the study of immunodominance and the factors which influence it. The S1 determinant of the HA molecule is one of eight identified non-overlapping T cell determinants on HA. A synthetic peptide comprising this T cell site (HA110-120), a panel of analogs containing single substitutions in this determinant, and homologs truncated at the amino- or carboxy-terminal were used to examine the fine specificities of 15 T cells specific for S1 in the context of I-E$\sp{\rm d}$. The results indicate that every residue within the minimal determinant plays a role in the T cell recognition process, as single substitutions at each of these positions affected the ability of the peptide to stimulate at least some S1 specific T cells. For the majority of the residues examined, substitutions had dissimilar effects on distinct T cells, indicating that the substituted residues were affecting recognition in a receptor specific manner. Each of the 15 T cells examined had a distinct reactivity pattern, suggesting that the BALB/c T cell repertoire for this site is to exceed 100 distinct clonotypes. To measure the extent that recognition of each determinant contributes toward the total response to HA in the course of an anti-viral immune response in vivo, synthetic peptides representing each of the eight determinants were used in a limiting dilution assay. Examination of the response of intranasally infected mice indicates that the proportion of T cells specific for distinct determinants can change during the course of an immune response. T cells specific for S2 became more dominant with time and, by day 15, made up more than 75% of the entire HA specific T cell response. In contrast to the T cell response induced by pulmonary infection, immunization of mice by intranasal inoculation with UV-inactivated virus did not result in the dominance of S2 specific T cells at any time point examined, suggesting that the composition of the T cell response can be influenced by the mode of immunization.

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Recommended Citation

Haberman, Ann Marie, "An analysis of the specificity and immunodominance of the T cell response to the hemagglutinin molecule of influenza virus" (1992). Dissertations available from ProQuest. AAI9308586.