Acid-induced conformational modification of the hemagglutinin molecule alters interaction of influenza virus with antigen-presenting cells.
Brief exposure of influenza virus to pH 5 was found to have extensive effects upon presentation of viral Th cell antigenic determinants. This acidity, comparable to that encountered in host cell endosomes, was known to effect conformational changes in the viral hemagglutinin (HA) which alter the molecule's fusion activity, antigenicity, and susceptibility to enzymes. Three major effects of low pH upon presentation of viral T cell determinants were observed: first, acid pretreatment permitted presentation by pre-fixed APC of two of three linear T cell sites of the HA molecule, bypassing the APC activity required to present untreated virus; second, the two determinants presented in this manner disappeared rapidly from APC surfaces; third, acid-pretreated virus was not efficiently utilized by active APC in the normal pathway of viral antigen presentation. These observations suggest that the pH-induced conformational transition of HA may constitute sufficient processing for certain linear determinants of the molecule and additionally influences the processes involved in the general formation and presentation of viral T cell sites.
Eisenlohr
L C
LC
Wistar Institute, Philadelphia, PA 19104.
Gerhard
W
W
Hackett
C J
CJ
D000085:Acetates; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D002951:Citrates; D000939:Epitopes / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000085:Acetates; D002951:Citrates; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D008562:Membrane Glycoproteins