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Eur J Immunol. 1989 Mar;19(3):523-8.

The structural requirements for class II (I-Ad)-restricted T cell recognition of influenza hemagglutinin: B cell epitopes define T cell epitopes.

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National Institute for Medical Research, Mill Hill, London, GB.


A majority of I-Ad-restricted CD4+ clones elicited by influenza X31 (H3N2) virus infection, recognize a synthetic peptide of hemagglutinin (HA) corresponding to an antibody binding region of the HA1 subunit (site B: HA1 177-199). The structural requirements for class II-restricted T cell recognition were investigated by determining the proliferative responses of representative CD4+ clones to truncated HA1 peptides and synthetic peptide analogues. Two distinct T cell epitopes were identified and CD4+ clones, specific for either determinant, were sensitive to the same single amino acid substitutions in synthetic peptides at HA1 193 S----N or HA1 198 A----E, that had featured in antigenic drift and abrogated antibody binding to native HA. Competitive inhibition studies, between stimulatory HA1 peptides and non-stimulatory analogue peptides, for antigen presentation to CD4+ clones established that the 193 S----N and 198 A----E substitutions could affect either interaction with the T cell receptor or class II molecule, according to the specificity of the CD4+ clone examined. The structural requirements for class II-restricted T cell recognition of the linear sequence determinants of HA are, therefore, integrally linked to conformation-dependent antibody recognition of the native molecule.

[Indexed for MEDLINE]

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