HEAT-INACTIVATED SENDAI-VIRUS CAN ENTER MULTIPLE MHC CLASS-I PROCESSING PATHWAYS AND GENERATE CYTOTOXIC T-LYMPHOCYTE RESPONSES IN-VIVO

We have earlier described an alternative MHC class I processing pathwa y for Sendai virus (SV) in H-2K(b)-transfected T2 cells (T2K(b)). Thes e cells have deleted genes for transporters associated with Ag process ing (TAP1/2) and proteasome subunits LMP2/7 but can still process SV f or the presentation of an immunodominant nucleoprotein CTL epitope (nu cleoprotein peptide 324-332, FAPGNYPAL, SV9), even in the presence of the fungal metabolite brefeldin A (BFA). Presently we have compared li ve and heat-inactivated SV to investigate whether infectious virus, in cluding early events such as binding and fusion at the host cell membr ane, is important for nonclassical MHC class I processing and immunoge nicity. We have found that heated virus (56 degrees C, boiled or autoc laved) with no fusion and hemagglutinin-neuraminidase activities, beha ves similar to live SV in T2K(b) cells by entering a TAP-independent a nd BFA-resistant pathway. In EL-4 cells, which do not express this non classical TAP-independent and BFA-resistant pathway, heat-treated SV i s processed in a BFA-sensitive way. in T1K(b)- and TAP1/2-transfected T2K(b) cells, as in T2K(b) cells, processing of heat-inactivated SV wa s completely BFA resistant. Heat-inactivated SV was also found to prim e CTLs in vivo. We conclude that heat-inactivated SV can enter both BF A-sensitive and -resistant MHC class I processing pathways and that SV in this respect may be particularly efficient. What property in the S V that is important for this characteristic is presently not clear but might be useful for the deliberate generation of CTL responses in viv o.