Genetic control and fine specificity of the immune response to a synthetic peptide of influenza virus hemagglutinin.
The immune response to a synthetic peptide, H3 HA1(305-328), representing the C'-terminal 24 amino acid residues of the HA1 chain of the hemagglutinin of the H3 subtype of influenza virus is controlled by genes in the I region of the major histocompatibility complex. Mice of the H-2d haplotype are high responders and produce antibody for several months after a single injection of peptide without carrier. Mice of the H-2b, H-2k, and H-2q haplotypes are low antibody responders. Investigation of recombinant and congenic mouse strains revealed that high responsiveness requires the genes that encode the I-Ed molecule. Immunoassays, involving direct binding to analogs of this peptide and inhibition by both these analogs and synthetic epitopes, were used to analyze the specificity of the polyclonal response. In BALB/c mice, the primary antibody response is directed principally against the antigenic site 314-LKLAT-318, whereas the secondary response after a boost is predominantly directed to a distinct site, 320-MRNVPEKQT-328. The T-cell response to the peptide H3 HA1(305-328), as measured by antigen-induced proliferation of primed T cells in vitro, is also I-Ed restricted in high-responder H-2d mice and is directed against an antigenic site that does not require the four C-terminal residues unique to the H3 influenza subtype. A different epitope appears to be recognized by T cells from CBA (H-2k) mice, which proliferate to a moderate extent on exposure to the peptide but, nevertheless, do not provide help for an antibody response.
Brown
L E
LE
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Murray
J M
JM
Anders
E M
EM
Tang
X L
XL
White
D O
DO
Tregear
G W
GW
Jackson
D C
DC
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D002642:Chick Embryo; D006183:H-2 Antigens / Q000032:analysis; D006389:Hemagglutinins, Viral / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D009980:Influenza A virus / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology
D006183:H-2 Antigens; D006389:Hemagglutinins, Viral; D064532:Histocompatibility Antigen H-2D