The structural requirements for class II (I-Ad)-restricted T cell recognition of influenza hemagglutinin: B cell epitopes define T cell epitopes.
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.
Graham
C M
CM
National Institute for Medical Research, Mill Hill, London, GB.
Barnett
B C
BC
Hartlmayr
I
I
Burt
D S
DS
Faulkes
R
R
Skehel
J J
JJ
Thomas
D B
DB
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000032:analysis*; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000945:Antigens, Differentiation, T-Lymphocyte; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II