title: TAP1-deficient mice select a CD8+ T cell repertoire that displays both diversity and peptide specificity.
abstract: Mice deficient in the gene encoding the transporter associated with antigen processing 1 (TAP1) are defective in providing major histocompatibility complex (MHC) class I molecules with cytosolic peptides. Consequently, these mice express reduced levels of MHC class I glycoproteins on the cell surface, and have reduced numbers of CD8+ T cells in the periphery. In the present study, we have addressed the diversity and specificity of the peripheral CD8+ T cell population in TAP1 -/- mice. CD8+ T cells were polyclonal with regard to T cell receptor (TCR) V beta expression. Overall, V beta usage in TAP1 -/- mice appear to be very similar to that in wild-type mice, with significantly reduced levels of V beta 5.1/5.2-expressing CD8+ T cells as the only clear exception. This polyclonal population of CD8+ T cells readily mounted epitope-specific CTL responses against four out of five well-defined MHC class I-restricted peptides. In contrast to allospecific CTL, peptide-specific CTL from TAP1 -/- mice did not cross-react on cells expressing normal levels of H-2b class I. The present results demonstrate that a polyclonal CD8+ T cell repertoire, displaying both diversity and peptide specificity, is positively selected in mice devoid of a functional peptide transporter. These observations imply that TAP-dependent peptides are not absolutely required for positive selection of a functionally diverse repertoire of CD8+ T cells.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
authors.forename: J K
authors.initials: JK
authors.lastname: Sandberg
authors.forename: B J
authors.initials: BJ
authors.lastname: Chambers
authors.forename: L
authors.initials: L
authors.lastname: Van Kaer
authors.forename: K
authors.initials: K
authors.lastname: Kärre
authors.forename: H G
authors.initials: HG
authors.lastname: Ljunggren
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000145:classification*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000939:Epitopes; D006183:H-2 Antigens; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse