NON-MHC GENES INFLUENCE VIRUS CLEARANCE THROUGH REGULATION OF THE ANTIVIRAL T-CELL RESPONSE - CORRELATION BETWEEN VIRUS CLEARANCE AND T-C AND T-D ACTIVITY IN SEGREGATING BACKCROSS PROGENY

To determine the mechanism by which non-MHC genes control the rate of virus clearance in mice infected with lymphocytic choriomeningitis vir us, a segregating backcross population was studied. Thirty BC1 animals were infected with virus, and virus-specific delayed-type hypersensit ivity (DTH) was followed by measurement of footpad swelling. Ten days after virus inoculation, the animals were sacrificed and spleen virus titer together with splenic T-c activity was measured. With regard to all three parameters a continuous distribution was observed in this ba ckcross population. However, using cutoff values based on parental and F-1 animals tested in parallel, 11/30 animals were assigned T-c respo nders, 23/30 DTH responders and 10/30 cleared virus with maximal effic iency. Comparison of responder status with regard to the different par ameters revealed a strong correlation between T-c responsiveness and t he ability to clear virus. Amongst T-c low responders a correlation be tween DTH reactivity and virus clearance was observed. Taken together, these results indicate that non-MHC genes affect virus clearance thro ugh regulation of the antiviral T-cell response, especially the virus- specific T-c response. However, also virus-specific DTH reactivity see ms important, particularly when T-c activity is low.