TAP1-deficient mice select a CD8+ T cell repertoire that displays both diversity and peptide specificity

Eur J Immunol. 1996 Feb;26(2):288-93. doi: 10.1002/eji.1830260203.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / immunology*
  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / classification*
  • Cytotoxicity, Immunologic / genetics
  • Dose-Response Relationship, Immunologic
  • Epitopes / analysis
  • Epitopes / immunology
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology
  • Immunophenotyping
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • T-Lymphocytes, Cytotoxic / classification
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • Epitopes
  • H-2 Antigens
  • TAP1 protein, human
  • Tap1 protein, mouse