The immune response of BALB/c mice to influenza hemagglutinin: commonality of the B cell and T cell repertoires and their relevance to antigenic drift.
An extensive analysis of the class II (I-Ad)-restricted T cell repertoire for influenza hemagglutinin (HA) of the H3 subtype, elicited by natural infection, has shown that majority of CD4+ memory T cell clones focus on antibody-binding regions of HA, sites B and E, and are sensitive to the residue substitutions that have occurred in these regions during antigenic drift. The proliferative responses of CD4+ clones to synthetic peptides have identified T cell epitopes within site B, HA1 177-199 and HA1 182-199, and site E. HA1 56-76. The recognition specificity of T cell clones for antibody-selected mutant viruses, with single amino acid substitutions within these recognition sites identified residues 63, 189, 193 and 198 as being important for T cell recognition and thus established that BALB/c, CD4+ T cell clones were sensitive to the same substitutions known to abrogate BALB/c antibody recognition of the native HA. Our findings indicate extensive commonality of the B cell and T cell repertoires for HA, which may be relevant to an understanding of the immune pressures for antigenic drift, and, moreover, suggest that the antigen-specific B memory cell may be instrumental in selection of the peripheral T cell repertoire.
Barnett
B C
BC
National Institute for Medical Research, Mill Hill, London, GB.
Graham
C M
CM
Burt
D S
DS
Skehel
J J
JJ
Thomas
D B
DB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D001666:Binding Sites, Antibody; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000032:analysis / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell