ENHANCED MHC CLASS II-RESTRICTED PRESENTATION OF MEASLES-VIRUS (MV) HEMAGGLUTININ IN TRANSGENIC MICE EXPRESSING HUMAN MV RECEPTOR CD46

This study analyzes the role of the measles virus (MV) receptor, i.e. the human CD46 molecule, in the MHC class II-restricted presentation o f MV hemagglutinin (H). We generated transgenic mice ubiquitously expr essing CD46, with a similar level of transgene expression on the surfa ce of antigen-presenting cells (APC), i.e. B cells, dendritic cells (D C) and macrophages. APC isolated from transgenic mice and nontransgeni c: controls were tested for their ability to present MV H to H-specifi c CD4(+) I-E-d-restricted T cell hybridomas. All three populations of APC were capable of presenting MV to T cell hybridomas, DC being the m ost efficient. Expression of CD46 on B lymphocytes increased MHC class II-dependent presentation of MV H up to 100-fold, while CD46-transgen ic UC stimulated H-specific T cell hybridomas up to 10-fold better tha n nontransgenic DC. Interestingly, expression of CD46 did not change t he presentation efficiency of transgenic macrophages, indicating that CD46-dependent enhancement of antigen presentation depends on the natu re of the APC. Furthermore, a single injection of UV-inactivated MV pa rticles into CD46-transgenic mice, but not nontransgenic controls, ind uced generation of MV-specific T lymphocytes and production of anti-H antibodies, suggesting a role for CD46 in the efficient capture of MV in vivo. These results show for the first time that one ubiquitously e xpressed cell surface receptor, like CD46, could function in receptor- mediated antigen presentation both in vitro and in vivo and its perfor mance depends on the type of APC which expresses it.