Stable expression of clonal specificity in murine cytomegalovirus-specific large granular lymphoblast lines propagated long-term in recombinant interleukin 2.

The somatic stability of cloned long-term cytolytic T lymphocyte lines (CTLL) specific for antigens encoded by murine cytomegalovirus (MCMV) was tracked for more than two years of continuous in vitro propagation. Clone S1 retained its original specificity for a structural (S) antigen of MCMV for about eight months in the presence of antigen and interleukin 2 (IL 2), but not in IL 2 alone. In the following months, however, in spite of the continued presence of antigen, clonal variants developed that displayed distinct patterns of target cell recognition, including loss of the original specificity and acquisition of exclusive specificity for the natural killer target cell YAC-1. On the other hand, large granular lymphoblast (LGL) lines, line IE1-IL and a series of sublines thereof, could be established that stably expressed Ld-restricted specificity for a viral nonstructural immediate-early (IE) antigen more than two years after withdrawal of antigen and feeder cells when propagated in the presence of pure recombinant human IL 2. The finding that the presence of antigen was not essential for the stability of clone IE1-derived CTLL indicates that maintenance of specificity in LGL lines is not a result of antigen-mediated selection, but reflects an intrinsic property.