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CD8-Mediated Intraepithelial Lymphocyte Snatching of Thymic Leukemia MHC Class Ib Molecules In Vitro and In Vivo¹

Nathalie Pardigon^*, Kazuyo Takeda^*, Bertrand Saunier^*, Felicita Hornung^*, James Gibbs^*, Andrea Weisberg^*, Nikhat Contractor, Brian Kelsall, Jack R. Bennink^* and Jonathan W. Yewdell^2,*

^* Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892; and Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892

Thymic leukemia (TL) is a MHC class Ib molecule that interacts with CD8 homodimers. CD8 is abundantly expressed by intraepithelial T lymphocytes (IELs) located in close proximity to TL-expressing intestinal epithelial cells. In this study, we show that CD8⁺ IELs "snatch" TL from the plasma membrane of TL-expressing cells and express TL in its proper orientation on their own cell surface. TL snatching is enhanced by cross-linking of IEL TCRs in a phosphatidylinositol kinase-dependent manner, and results in overall alterations to the IEL cell surface detected by enhanced binding of peanut agglutinin lectin. Induction of bowel inflammation results in the presence of TL on IELs, probably via in vivo snatching, providing the initial evidence for the interaction of CD8 IELs with intestinal cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

² Address correspondence and reprint requests to Dr. Jonathan W. Yewdell, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 211, Building 4, 4 Center Drive, Bethesda, MD 20892-0440. E-mail address: jyewdell{at}nih.gov

³ Abbreviations used in this paper: TL, thymus leukemia; IEL, intraepithelial T lymphocyte; PNA, lectin peanut agglutinin; LN, lymph node; EM, electron microscopy; o/n, overnight.

⁴ The online version of this article contains supplemental material.

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