An analysis of the properties of monoclonal antibodies directed to epitopes on influenza virus hemagglutinin

1990 ◽  
Vol 114 (1-2) ◽  
pp. 1-26 ◽  
Author(s):  
L. E. Brown ◽  
J. M. Murray ◽  
D. O. White ◽  
D. C. Jackson
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Influenza Virus Hemagglutinin

scholarly journals Influenza virus hemagglutinin trimers and monomers maintain distinct biochemical modifications and intracellular distribution in brefeldin A-treated cells.

1991 ◽  
Vol 2 (7) ◽  
pp. 549-563 ◽  
Author(s):  
G Russ ◽  
J R Bennink ◽  
T Bächi ◽  
J W Yewdell
Keyword(s):  
Endoplasmic Reticulum ◽  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Golgi Complex ◽  
Brefeldin A ◽  
Retrograde Transport ◽  
Cell Fractionation ◽  
Influenza Virus Hemagglutinin ◽  
Infected Cells ◽  
Vesicular Compartment

Brefeldin A (BFA) induces the retrograde transport of proteins from the Golgi complex (GC) to the endoplasmic reticulum (ER). It is uncertain, however, whether the drug completely merges the ER with post-ER compartments, or whether some of their elements remain physically and functionally distinct. We investigated this question by the use of monoclonal antibodies specific for monomers and trimers of the influenza virus hemagglutinin (HA). In untreated influenza virus-infected cells, monomers and trimers almost exclusively partition into the ER and GC, respectively. In BFA-treated cells, both monomers and trimers are detected in the ER by immunofluorescence. Cell fractionation experiments indicate, however, that whereas HA monomers synthesized in the presence of BFA reside predominantly in vesicles with a characteristic density of the ER, HA trimers are primarily located in lighter vesicles characteristic of post-ER compartments. Biochemical experiments confirm that in BFA-treated cells, trimers are more extensively modified than monomers by GC-associated enzymes. Additional immunofluorescence experiments reveal that in BFA-treated cells, HA monomers can exist in an ER subcompartment less accessible to trimers and, conversely, that trimers are present in a vesicular compartment less accessible to monomers. These findings favor the existence of a post-ER compartment for which communication with the ER is maintained in the presence of BFA and suggest that trimers cycle between this compartment and the ER, but have access to only a portion of the ER.

scholarly journals Idiotypy of clonal responses to influenza virus hemagglutinin.

1981 ◽  
Vol 154 (5) ◽  
pp. 1525-1538 ◽  
Author(s):  
Y N Liu ◽  
C A Bona ◽  
J L Schulman
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Binding Sites ◽  
Cross Reactivity ◽  
Secondary Response ◽  
Antigenic Determinants ◽  
Antiviral Responses ◽  
Influenza Virus Hemagglutinin ◽  
The Cross

Anti-idiotype antisera were raised in syngeneic (BALB/c mice) and homologous (A/J mice) systems to study the cross-reactive idiotypes among monoclonal antibodies to PR8 and B/Lee virus HA and the expression of these idiotypes during primary and secondary antiviral responses of BALB/c mice. Extensive idiotypic cross-reactivity was demonstrated among monoclonal antibodies specific for distinct antigenic determinants on PR8 hemagglutinin (HA). The study of idiotypy of monoclonal antibodies against the same or overlapping antigenic determinants on B/Lee HA showed that these monoclonal antibodies may bear (a) a true individual idiotype not shared by other monoclonal antibodies, (b) idiotypes shared by few monoclonal antibodies, and (c) true cross-reactive idiotypes shared by all of these monoclonal antibodies. In contrast, no cross-reactive idiotypes were detectable among monoclonal antibodies to B/Lee HA and monoclonal antibodies to PR8 HA. Furthermore, we have shown that the anti-idiotype antibodies we used recognize determinants on monoclonal antibodies closely associated with antigenic binding sites. Finally, studies of the idiotypes expressed during primary and secondary antiviral HA responses of mice immunized with B/Lee virus revealed persistence of some idiotypes during both primary and secondary responses, whereas others were only expressed in the primary or secondary response.

scholarly journals Identification of antibodies targeting the H3N2 hemagglutinin receptor binding site following vaccination of humans

2019 ◽  
Author(s):  
Seth J. Zost ◽  
Juhye Lee ◽  
Megan E. Gumina ◽  
Kaela Parkhouse ◽  
Carole Henry ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Antigenic Sites ◽  
Influenza Virus Hemagglutinin ◽  
Ha Protein

SUMMARYAntibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly-reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identified several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that were sensitive to substitutions in conventional antigenic sites and were not broadly-reactive. However, we also identified one H3N2 HA RBS-targeting mAb that was exceptionally broadly reactive despite being sensitive to substitutions in residues outside of the RBS. We determined that similar antibodies are present at measurable levels in the sera of some individuals but that they are inefficiently elicited by conventional vaccines. Our data indicate that some HA RBS-targeting antibodies can be surprisingly effective against variable viral strains even if they are somewhat sensitive to substitutions in HA residues adjacent to the RBS.

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