THYMUS LEUKEMIA ANTIGEN INTERACTS WITH T-CELLS AND SELF-PEPTIDES

The functional role of the class Ib thymus-leukemia (TL) Ag expressed within the thymic cortex and intestinal mucosa of the mouse remains un known, In an approach to elucidate the potential functionality of TL, we developed transgenic mice that ectopically express the H-2T18(d) ge ne product on essentially all nucleated cells through the control of a heterologous H-2K(b) gene promoter, Transgenic mice demonstrated an i ncrease in the number of CD4(+) lymphocytes within the thymus and lymp h nodes; these cells displayed an altered T cell receptor repertoire p ossibly suggesting a role for the ectopically expressed TL protein, Th e TL protein additionally displayed the characteristics of a bona fide transplantation Ag, because skin grafts from transgenic animals onto MHC- and minor histocompatibility Ag-matched nontransgenic recipient m ice resulted in a rapid and vigorous immunologic rejection of the allo graft, In MLR studies, transgenic stimulator cells induced the prolife ration of responders to a level intermediate between genetically ident ical and H-2-disparate responder-stimulator combinations. The TL prote in was also capable of stimulating cytotoxic T lymphocytes, thereby re sulting in specific lysis of TL(+) target cells, Further data demonstr ated that the TL protein assembles with peptides that are modified at the amino terminus, and that TL retains these molecules at the cell su rface, Together, these data suggest that H-2T18(d) is capable of inter acting with T cells via a bound peptide, These data further support th e possibility that TL may subserve a specialized function within the i mmunologic system.