TCR-BETA TRANSGENIC MICE FAIL TO MEDIATE A GVHR DUE TO DEFECTS OF ALLORECOGNITION AND SUBSEQUENT IL-2 GENERATION

All T cells of TCR-beta transgenic mice bear a single TCR-beta chain a nd consequently the diversity of the TCR may be reduced by as much as one million-fold, Despite this limited diversity, many measures of lym phocyte function in these mice are normal, We have previously demonstr ated that Lymphoid cells from TCR-beta mice are unable to mediate an i ntense graft-versus-host response (GVHR). In order to investigate the mechanism of this hyporesponsiveness, we studied in vivo allorecogniti on in diverse strains of TCR-beta mice, All tested strains of TCR-beta mice failed to mediate a substantial GVHR across multiple H-2 barrier s, In addition, mixtures of cells from several strains of TCR-beta mic e only generated mild GVHRs, Sensitive tests of in vitvo allorecogniti on show that lymphoid cells from TCR-beta mice respond less vigorously to alloantigen as measured both by decreased proliferation and decrea sed IL-2 production in a MLR, In addition, cells from TCR-beta mice fa il to use exogenous IL-2 appropriately in their response to alloantige n. We conclude that the fixed TCR-beta chain causes a defective respon se to alloantigen, which is measured as decreased IL-2 generation and utilization, and that this abnormality results in a decreased GVHR.