Qa-2-dependent selection of CD8α/α T cell receptor α/β+ cells in murine intestinal intraepithelial lymphocytes

Gobardhan Das, Dina S. Gould, Mathew M. Augustine, Gladis Fragoso, Edda Sciutto, Iwona Stroynowski, Luc Van Kaer, Danny J. Schust, Hidde Ploegh, Charles A. Janeway

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Murine intestinal intraepithelial lymphocytes (iIELs) are made up of a heterogeneous mix of T cells with unique phenotypes. Whereas CD8+ T cells in peripheral lymphoid organs use CD8α/β and are selected on MHC class Ia molecules, a majority of iIELs use CD8α/α. Here, we report that the presence of CD8α/α TCR-α/β cells in iIELs is independent of classical MHC class I molecules Kb and Db, as illustrated by their presence in Kb/Db double-knockout mice and in mice lacking a nonclassical MHC class I molecule, CD1d. Most strikingly, their presence is decreased by ~70% in mice lacking transporter associated with antigen processing (TAP). The TAP-dependent nonclassical MHC class I molecule Qa-2 is strongly implicated in the presence of these cells, as inferred from the low numbers of CD8α/α TCR-α/β T cells in mice deficient in Qa-2 genes. Second, a Qa-2-transgenic mouse made in a Qa-2- strain showed an increase in the numbers of CD8α/α cells among its iIELs. Thus, the presence of CD8α/α TCR-α/β cells in iIELs is mainly dependent on the nonclassical MHC class I molecule Qa-2.

Original languageEnglish (US)
Pages (from-to)1521-1527
Number of pages7
JournalJournal of Experimental Medicine
Volume192
Issue number10
DOIs
StatePublished - Nov 20 2000

Keywords

  • CD8α/α TCR-α/β cells
  • Intestinal intraepithelial lymphocyte
  • MHC class I-deficient mice
  • Qa-2-deficient mice
  • Qa-2-transgenic mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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