Virus recognition by specific natural antibodies and complement results in MHC I cross-presentation

Natural antibodies (NAb) and complement (C') are important regulators of immune system activation. We have shown previously that the galactosyl-alpha l,3-galactosyl (Gal alpha l,3Gal) xenoantigen and the similar ABO histo-blood group antigens are transferred onto virus from the producer cell, resulting in sensitisation of the virus to the respective NAb in a C'-dependent manner. Here we show that measles virus (Mv) that expresses Gal alpha,1,3Gal termini can drive the proliferation of human Tcells in the presence of serum and autologous DC, whereas without such targets, measles, as expected, suppress T cell reactivity. The use of affinity-purified NAb to Galal,3Gal and rabbit C' demonstrated the components in human serum responsible for this effect. Proteasome inhibition and blocking of antigen presentation showed that the increased T cell proliferation was mediated by MHC class I cross-presentation of immune complexes. These results lend further support to the idea that polymorphic carbohydrates of the Gal alpha,1,3Gal/ABO type serve as important targets for NAb and C' and that their expression on virus has influenced their evolution by contributing to protection against viral transmission within as well as between species. The adjuvance effect of this recognition, acting as a bridge between the natural innate. and adaptive immune systems, also has important implications for vaccine development.