title: Role of receptor-binding activity of the viral hemagglutinin molecule in the presentation of influenza virus antigens to helper T cells.
abstract: The concentration of antigen required to stimulate influenza virus-specific helper T cells was observed to be dependent upon the antigenic form bearing the relevant determinant: intact, nonreplicative virus was needed only in picomolar amounts, while denatured proteins, protein fragments, or synthetic peptides were required in micromolar concentrations for a threshold level of stimulation. Antigenic efficiency of intact virus was found to result from the attachment of virus to sialic acid residues on the surface of the antigen-presenting cell since spikeless viral particles lacking the hemagglutinin molecule were much less efficient antigens for helper T cells and continuous presence of hemagglutination-inhibiting antihemagglutinin antibodies reduced efficiency of stimulation by intact virus approximately 100-fold for both hemagglutinin and internal virion proteins. Influenza virus associated rapidly with antigen-presenting cells; less than 10 min at 20 degrees C was sufficient to introduce virus for a maximal level of T-cell stimulation. This rapid attachment was blocked by antibodies to the hemagglutinin or by pretreatment of the antigen-presenting cells with neuraminidase to remove the cellular virus receptor. Following viral adsorption by antigen-presenting cells, a lag period of 30 min at 37 degrees C was required for the expression of helper T-cell determinants. One early event identified was the movement of the virus to a neuraminidase-insensitive compartment, which can occur at 10 degrees C, but which was not equivalent to expression of helper T-cell determinants. Preincubation of cells with virus at 10 degrees C for 4 h reduced the lag period of helper T-cell determinant expression to 15 min when these cells were shifted to 37 degrees C, suggesting that transition of the virus to a neuraminidase-resistant state is a required step in presentation of T-cell antigenic determinants.
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002999:Clone Cells; D004306:Dose-Response Relationship, Immunologic; D006389:Hemagglutinins, Viral / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D011971:Receptors, Immunologic / Q000276:immunology; D012794:Sialic Acids / Q000502:physiology; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D006389:Hemagglutinins, Viral; D007376:Interleukin-2; D011971:Receptors, Immunologic; D012794:Sialic Acids