Branched polypeptides as antigens for influenza virus hemagglutinin and T-cell receptor subunits.
The multiple antigenic peptide (MAP) method was applied to improve the immunogenicity of synthetic peptides representing distinct regions of the influenza virus hemagglutinin (HA). A tetrameric MAP with multiply incorporated overlapping B- and T-cell epitopes was combined with a particular HA sequence representing the slightly modified fusion peptide on the C-terminus of the Lys core (MAP-1). As a result of repeated injections of BALB/c mice with MAP-1 but not with the monomeric HA1C[Arg] peptide, the appearance of MAP-1-specific antibodies crossreactive with the acid-pretreated virus could be observed. In vitro studies revealed the potency of the MAP-1 structure to induce proliferation of HA1C[Arg]-primed T-cells, and in vivo studies demonstrated the protective feature of the immune response elicited by MAP-1 and to a lesser extent by the monomeric HA1C[Arg]. The increased level of MAP-1 specific antibodies upon viral challenge shows the activation of MAP-1-specific B- and/or T-cells. The advantage of the previously verified FP3 helper T-cell epitope included in MAP-1 was further utilized to synthesize chimeric structures comprising short fragments of the zeta of (MAP-2) or delta (MAP-3) subunits of the T-cell antigen receptor (TCR) complex. The selected peptides of the zeta and delta-chain regions failed to elicit an antibody response in BALB/c mice as tetra- or octamers, but the inclusion of the modified fusion region resulted in an immunogenic construction.(ABSTRACT TRUNCATED AT 250 WORDS)
Tóth
G K
GK
A. Szent-Györgyi Medical University, Szeged, Hungary.
Váradi
G
G
Nagy
Z
Z
Monostori
E
E
Penke
B
B
Hegedüs
Z
Z
Andó
I
I
Fazekas
G
G
Kurucz
I
I
Mák
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000276:immunology*
D000906:Antibodies; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D008565:Membrane Proteins; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; C054979:antigen T cell receptor, zeta chain