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 Vbeta diversity <1% that of wild-type mice and quasimonoclonal (QM) mice with oligoclonal B cells and TCR Vbeta 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%.
AbuAttieh
Mouhammed
M
Transplantation Biology Program, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Rebrovich
Michelle
M
Wettstein
Peter J
PJ
Vuk-Pavlovic
Zvezdana
Z
Limper
Andrew H
AH
Platt
Jeffrey L
JL
Cascalho
Marilia
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics / Q000276:immunology*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis / Q000235:genetics / Q000276:immunology; D011010:Pneumocystis / Q000276:immunology; D016720:Pneumocystis Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous
D016693:Receptors, Antigen, T-Cell, alpha-beta