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Qa-2–dependent Selection of CD8/ T Cell Receptor /ß⁺ Cells in Murine Intestinal Intraepithelial Lymphocytes

Correspondence to: Charles A. Janeway, Jr., Section of Immunobiology, P.O. Box 208011, LH416, 310 Cedar St., New Haven, CT 06520-8011. Tel:203-785-2793 Fax:203-737-1765

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 CD8/ß and are selected on MHC class Ia molecules, a majority of iIELs use CD8/. Here, we report that the presence of CD8/ TCR-/ß cells in iIELs is independent of classical MHC class I molecules K^b and D^b, as illustrated by their presence in K^b/D^b 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 CD8/ TCR-/ß 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 CD8/ cells among its iIELs. Thus, the presence of CD8/ TCR-/ß cells in iIELs is mainly dependent on the nonclassical MHC class I molecule Qa-2.

Key Words: CD8/ TCR-/ß cells, MHC class I–deficient mice, Qa-2–transgenic mice, Qa-2–deficient mice, intestinal intraepithelial lymphocyte

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