Selection and expansion of CD8α/α+ T cell receptor α/β+ intestinal intraepithelial lymphocytes in the absence of both classical major histocompatibility complex class I and nonclassical CD1 molecules

Se Ho Park, Delphine Guy-Grand, François A. Lemonnier, Chyung Ru Wang, Albert Bendelac, Bana Jabri

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Intestinal intraepithelial lymphocytes (IELs) in mice include two main subsets of TCR-α/β+ cells which differ functionally and ontogenically from each other. One expresses the CD8α/α homodimer, whereas the other expresses the CD8α/β heterodimer. Although the presence of all CD8+TCR-α/β+ IELs is dependent on β2-microglobulin molecules, the nature of the major histocompatibility complex (MHC) class I molecules recognized by the CD8α/α and the CD8α/β+ subsets has remained elusive. Using mutant mice lacking the expression of both H2Kb and H2-Db, we show that the CD8α/β+TCR- α/β+ subset is dependent on K or D molecules, whereas the CD8α/α+TCR- α/β+ subset is independent of classical MHC class I molecules. Furthermore, the CD8α/α+ cells are conserved in mice lacking expression of CD1, a nonclassical MHC class I-like molecule previously proposed to be a potential ligand for IELs. Using transporter associated with antigen processing (TAP)-deficient mice, this cell population can be further separated into a TAP-dependent and a TAP-independent subset, suggesting either the recognition of two nonclassical MHC-like molecules, only one of which is TAP dependent, or the involvement of a single nonclassical MHC-like molecule that is only partially TAP dependent. These findings demonstrate that CD8α/β+TCR-α/β+ IELs are restricted by H-2K and H-2D molecules, whereas the unusual subset of CD8α/α+TCR-α/β+ resident IELs recognize nonclassical MHC class I-like molecules that are distinct from CD1.

Original languageEnglish
Pages (from-to)885-890
Number of pages6
JournalJournal of Experimental Medicine
Volume190
Issue number6
DOIs
Publication statusPublished - 1999 Sep 20

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Keywords

  • CD1
  • CD8
  • Gene-targeted mouse
  • Intestinal intraepithelial lymphocytes
  • Major histocompatibility complex

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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