title: Clonal Deletion Prunes but Does Not Eliminate Self-Specific αβ CD8(+) T Lymphocytes.
abstract: It has long been thought that clonal deletion efficiently removes almost all self-specific T cells from the peripheral repertoire. We found that self-peptide MHC-specific CD8(+) T cells in the blood of healthy humans were present in frequencies similar to those specific for non-self antigens. For the Y chromosome-encoded SMCY antigen, self-specific T cells exhibited only a 3-fold lower average frequency in males versus females and were anergic with respect to peptide activation, although this inhibition could be overcome by a stronger stimulus. We conclude that clonal deletion prunes but does not eliminate self-specific T cells and suggest that to do so would create holes in the repertoire that pathogens could readily exploit. In support of this hypothesis, we detected T cells specific for all 20 amino acid variants at the p5 position of a hepatitis C virus epitope in a random group of blood donors.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Hematology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Wong
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Peter J R
authors.initials: PJ
authors.lastname: Ebert
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kidd
authors.affiliation: INSERM, UMR1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France and Université Toulouse III Paul-Sabatier, 31024 Toulouse, France.
authors.forename: Sabina
authors.initials: S
authors.lastname: Müller
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Peder J
authors.initials: PJ
authors.lastname: Lund
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Juang
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Keishi
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tse
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Birnbaum
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Evan W
authors.initials: EW
authors.lastname: Newell
authors.affiliation: Department of Pediatric Endocrinology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Darrell M
authors.initials: DM
authors.lastname: Wilson
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Gijsbert M
authors.initials: GM
authors.lastname: Grotenbreg
authors.affiliation: INSERM, UMR1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France and Université Toulouse III Paul-Sabatier, 31024 Toulouse, France.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valitutti
authors.affiliation: Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Quake
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: mmdavis@stanford.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
mesh_terms: D000818:Animals; D000940:Antigenic Variation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D017637:Clonal Deletion; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D017634:Self Tolerance / Q000276:immunology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta