Virus entry and antigen biosynthesis in the processing and presentation of class-II MHC-restricted T-cell determinants of influenza virus

Abstract

Receptor-mediated uptake of influenza virus is responsible for efficient introduction of virus particles to APC. This leads to the effective presentation to T-cells of very small concentrations of proteins entering on the intact virus. Endocytosed virus transits rapidly to the endosome compartment. Entry into this environment appears to greatly affect the fate of T-cell determinants. While promoting the presentation of determinants which require extensive antigen processing, the intracellular environment appears also to lead to destruction of labile determinants, such as those of NA. The same NA determinants are efficiently presented by actively infected cells, indicating that newly biosynthesized viral proteins need not be subjected to the same handling as internalized viral particles. In a similar way, site 3 of HA, which, in a single pulse of noninfectious virus or isolated HA protein is expressed with a relatively short half-life, has greatly improved levels of duration and expression on actively infected APC. Since certain T(H) determinants are unavailable or poorly expressed when introduced on nonreplicative influenza virus, vaccination with inactivated virus might have limitations in stimulating T(H) as well as class-I responses. Finally, individual T-cell determinants of the same protein can exhibit distinct patterns of expression and persistence on APC surfaces. These different half-lives of T(H) determinants may be influential in determining immuno-dominance of T-cell sites. Determinants that are longer-lived on APC may have a greater probability of interacting with appropriate T(H) precursors, which could lead to an enhanced T-cell response to that region of the viral protein.