Fitness of cell-mediated immunity independent of repertoire diversity

Fitness of cell-mediated immunity is thought. to depend on TCR diversity; however, this concept has not been tested formally. We tested the concept using JH(-/-) mice that lack B cells and have TCR V beta diversity < 1% that of wild-type mice and quasimonoclonal (QM) mice with oligoclonal B cells and TCR V beta diversity 7% that of wild-type mice. Despite having a TCR repertoire contracted > 99% and defective lymphoid organogenesis, JH(-/-) mice rejected H-Y-incompatible skin grafts as rapidly as wild-type mice. JH(-/-) mice exhibited T cell priming by peptide and delayed-type hypersensitivity, although these responses were less than normal owing either to TCR repertoire contraction or defective lymphoid organogenesis. QM mice with TCR diversity contracted > 90%, and normal lymphoid organs rejected H-Y incompatible skin grafts as rapidly as wild type mice and exhibited normal T cell priming and normal delayed-type hypersensitivity reactions. QM mice also resisted Pneumocystis murina like wild-type mice. rhus, cell-mediated immunity can function normally despite contractions of TCR diversity > 90% and possibly > 99%.