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Fitness of Cell-Mediated Immunity Independent of Repertoire Diversity¹

Mouhammed AbuAttieh^*,, Michelle Rebrovich^*, Peter J. Wettstein^,, Zvezdana Vuk-Pavlovic, Andrew H. Limper, Jeffrey L. Platt^*,,,¶ and Marilia Cascalho^2,*,,

^* Transplantation Biology Program, Department of Surgery, Department of Immunology, Department of Biochemistry and Molecular Biology, and ^¶ Department of Pediatrics, Mayo Clinic College of Medicine, Rochester, MN 55905

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 diversity <1% that of wild-type mice and quasimonoclonal (QM) mice with oligoclonal B cells and TCR V 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. Thus, cell-mediated immunity can function normally despite contractions of TCR diversity >90% and possibly >99%.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI48602 and HL79067.

² Address correspondence and reprint requests to Dr. Marilia Cascalho, Mayo Clinic, 200 First Street Southwest, Medical Sciences 2-75, Rochester, MN 55905. E-mail address: cascalho.marilia{at}mayo.edu

³ Abbreviations used in this paper: QM, quasimonoclonal; IGMT, ImMunoGeneTics information system; PADRE, Pan DR reactive epitope.

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