EFFICIENT MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-RESTRICTED PRESENTATION OF MEASLES-VIRUS RELIES ON HEMAGGLUTININ-MEDIATED TARGETING TO ITS CELLULAR RECEPTOR HUMAN CD46 EXPRESSED BY MURINE B-CELLS

Measles virus after binding to its cell surface human CD46 receptor fu ses with the plasma membrane. This fusion results in envelope hemagglu tinin (H) and fusion glycoprotein (F) incorporated into the plasma mem brane and injection of the nucleocapsid made of nucleoprotein (NP) int o the cytosol. The influence of targeting measles virus (MV) to CD46 i n the processing and presentation of MV H and NP to antigen specific M HC class II I-E(d) and I-A(d)-restricted T cell hybridomas was explore d using murine M12-CD46 B cell transfectants. Parent M12 cells, which lack any MV receptor, were unable to present any of these two viral pr oteins when incubated with MV particles. Incubating M12.CD46 cells wit h 200 ng and 10 mu g of MV could strongly stimulate H-specific and NP- specific T cells, respectively. Neosynthesis of MV proteins was not ne cessary since the efficiency of antigen presentation was similar when using ultraviolet-inactivated MV. Similar enhancing effects (more than 1,000-fold) on antigen presentation were also observed when using pur ified native H soluble or incorporated into liposomes whereas denatura ting H glycoprotein resulted in a poor efficiency in T cell stimulatio n, M12.CD46 being no more potent than the parental M12 counterpart. MV H and NP presentation efficiency did not depend on MV fusion with pla sma membrane as revealed by the lack of effect of specific fusion inhi bitors. Both MV H and NP presentations were sensitive to chloroquine i nhibition indicating that antigens from CD46-mediated captured MV were likely processed in the endosome/lysosome compartment. Altogether the se data indicate that (a) MV targeting via CD46 has a strong effect on the efficiency of antigen presentation by MHC class II, (b) the effec t is mediated by the binding of H to CD46, and (c) though MV does fuse with plasma membrane, endocytosis, and processing of virus particles are also occurring. Since, in humans, CD46 is expressed in almost ever y tissue including professional antigen-presenting cells, such a targe ting is likely to play a crucial role in the CD4(+) T cell-mediated pr imary immune response against the pathogen in vivo.