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 fuses with the plasma membrane. This fusion results in envelope hemagglutinin (H) and fusion glycoprotein (F) incorporated into the plasma membrane and injection of the nucleocapsid made of nucleoprotein (NP) into the cytosol. The influence of targeting measles virus (MV) to CD46 in the processing and presentation of MV H and NP to antigen specific MHC class II I-E(d)- and I-A(d)-restricted T cell hybridomas was explored using murine M12-CD46 B cell transfectants. Parent M12 cells, which lack any MV receptor, were unable to present any of these two viral proteins when incubated with MV particles. Incubating M12.CD46 cells with 200 ng and 10 micrograms of MV could strongly stimulate H-specific and NP-specific T cells, respectively. Neosynthesis of MV proteins was not necessary 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 purified native H soluble or incorporated into liposomes whereas denaturating H glycoprotein resulted in a poor efficiency in T cell stimulation, M12.CD46 being no more potent than the parental M12 counterpart. MV H and NP presentation efficiency did not depend on MV fusion with plasma membrane as revealed by the lack of effect of specific fusion inhibitors. Both MV H and NP presentations were sensitive to chloroquine inhibition indicating that antigens from CD46-mediated captured MV were likely processed in the endosome/lysosome compartment. Altogether these data indicate that (a) MV targeting via CD46 has a strong effect on the efficiency of antigen presentation by MHC class II, (b) the effect 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 every tissue including professional antigen-presenting cells, such a targeting is likely to play a crucial role in the CD4+ T cell-mediated primary immune response against the pathogen in vivo.
Gerlier
D
D
Laboratoire d'Immunobiologie Moléculaire, UMR 49, Centre National de la Recherche Scientifique-Ecole Normale Supérieure de Lyon, France.
Trescol-Biémont
M C
MC
Varior-Krishnan
G
G
Naniche
D
D
Fugier-Vivier
I
I
Rabourdin-Combe
C
C
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006389:Hemagglutinins, Viral / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008459:Measles virus / Q000276:immunology* / Q000502:physiology; D051916:Membrane Cofactor Protein; D008561:Membrane Fusion / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D014759:Viral Envelope Proteins / Q000276:immunology
D015703:Antigens, CD; D000956:Antigens, Viral; C497857:CD46 protein, human; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins