Activation of Lyt-2 associated with distant upstream insertion of an SL3-3 provirus

Two Lyt-2+ mutants of the T-cell lymphoma SL12.4.10 were selected by fluorescence activated cell sorting. Both mutants expressed Lyt-2 (CD8 alpha-chain) but not Lyt-3 (CD8 beta-chain). Derivatives of one Lyt-2+ mutant that expressed Lyt-3 could be isolated by sorting for Lyt-3+ cells. Southern blotting analysis indicated that both mutants had structural rearrangements within or immediately 3' of the Lyt-3 gene, accompanied by demethylation of at least one Hpa II site within the Lyt-2 gene. Gene cloning analysis of one mutant demonstrated that the structural rearrangement was due to insertion of an SL3-3 provirus 35 kb 5' to the Lyt-2 gene. It is likely that Lyt-2 gene activation is a direct or indirect consequence of proviral insertion at this site.