The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online 20 November 2000.
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© The Rockefeller University Press, 0022-1007/2000/11/1521/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 10, November 20, 2000 1521-1528

Brief Definitive Report

Qa-2–Dependent Selection of Cd8{alpha}/{alpha} T Cell Receptor {alpha}/β+ Cells in Murine Intestinal Intraepithelial Lymphocytes

Gobardhan Dasa, Dina S. Gouldb, Mathew M. Augustinea, Gladis Fragosoe, Edda Scittoe, Iwona Stroynowskid, Luc Van Kaerc, Danny J. Schustb, Hidde Ploeghb, and Charles A. Janeway, Jr.a

a Section of Immunobiology, Yale University School of Medicine, and the Howard Hughes Medical Institute, New Haven, Connecticut 06520-8011
b Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115
c Department of Microbiology and Immunology and The Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
d Center for Immunology and the Department of Microbiology and the Department of Internal Medicine, Southwestern Medical Center, Dallas, Texas 75235-9093
e Department of Immunology, Instituto de Investigaciones Biomedicas, Universidad Nacional Avtonoma de Mexico, Mexico D.F. 04510
Section of Immunobiology, P.O. Box 208011, LH416, 310 Cedar St., New Haven, CT 06520-8011.203-737-1765203-785-2793

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{alpha}/β and are selected on MHC class Ia molecules, a majority of iIELs use CD8{alpha}/{alpha}. Here, we report that the presence of CD8{alpha}/{alpha} TCR-{alpha}/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 CD8{alpha}/{alpha} TCR-{alpha}/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 CD8{alpha}/{alpha} cells among its iIELs. Thus, the presence of CD8{alpha}/{alpha} TCR-{alpha}/β cells in iIELs is mainly dependent on the nonclassical MHC class I molecule Qa-2.

Key Words: CD8{alpha}/{alpha} TCR-{alpha}/β cells • MHC class I–deficient mice • Qa-2–transgenic mice • Qa-2–deficient mice • intestinal intraepithelial lymphocyte

© 2000 The Rockefeller University Press


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