NAIVE CD4(-CELLS CONFER IDIOTYPE-SPECIFIC TUMOR RESISTANCE IN THE ABSENCE OF ANTIBODIES() T)

CD4(+) T cells can recognize a processed idiotypic peptide derived fro m the mouse lambda 2(315) immunoglobulin light chain. The idiotypic pe ptide is presented on the I-E(d) class II major histocompatibility com plex molecule. Mice made transgenic for a lambda 2(315)-specific alpha beta T cell receptor have been demonstrated to be specifically resist ant against a tumor challenge with the MOPC315 (alpha, lambda 2(315)) plasmacytoma (Lauritzsen, G. F, Weiss, S., Dembic, Z. and Bogen, B., P roc. Natl. Acad. Sci. USA 1994, 91: 5700). That study, however, did no t rule out a role of either anti-Id antibodies or T cells expressing n ontransgenic specificities due to expression of endogenous T cell rece ptor (TcR) alpha chains. Also, the role of different T cell subsets in protection was unclear. To remove these ambiguities, we have now made the transgenic mice homozygous for the scid mutation, known to inhibi t both Ig and TcR gene rearrangements. Such transgenic SCID mice lack B cells and antibodies while they still have plenty of CD4(+) and CD4( -)8(-) cells expressing the transgenic alpha beta T cell receptor. The number of CD8(+) T cell is dramatically reduced. Even so, transgenic SCID mice are protected against a challenge with MOPC315 plasmacytoma cells. Therefore, B cells, as well as novel T cell receptor specificit ies created by rearrangements of endogenous alpha-chain genes, are bot h dispensable for effective immunosurveillance in our system. Surprisi ngly, we found that transgenic CD8(+) and CD4(-)8(-) cells are idiotyp e-specific and I-E(d) restricted. However, these T cell subsets are no t required for resistance because adoptive transfer experiments demons trated that highly purified transgenic SCID CD4(+) cells suffice for t umor protection.