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Brief Definitive Report

Selection and Expansion of CD8/¹ T Cell Receptor /β¹ Intestinal Intraepithelial Lymphocytes in the Absence of Both Classical Major Histocompatibility Complex Class I and Nonclassical Cd1 Molecules

^a Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544
^b Hôpital Necker Enfants Malades, INSERM U429, 75015 Paris, France
^c Institut Pasteur, Unité d'Immunité Cellulaire Antivirale, 75015 Paris, France
^d Department of Pathology, Gwenn Knapp Center for Lupus and Immunological Research, University of Chicago, Chicago, Illinois 60637
Department of Molecular Biology, Princeton University, Princeton, NJ 08544.609-258-2205609-258-5351

bjabri{at}molbio.princeton.edu

Intestinal intraepithelial lymphocytes (IELs) in mice include two main subsets of TCR-/β¹ cells which differ functionally and ontogenically from each other. One expresses the CD8/ homodimer, whereas the other expresses the CD8/β heterodimer. Although the presence of all CD8⁺TCR-/β¹ IELs is dependent on β2-microglobulin molecules, the nature of the major histocompatibility complex (MHC) class I molecules recognized by the CD8/ and the CD8/β¹ subsets has remained elusive. Using mutant mice lacking the expression of both H2-K^b and H2-D^b, we show that the CD8/β¹TCR-/β¹ subset is dependent on K or D molecules, whereas the CD8/¹TCR-/β¹ subset is independent of classical MHC class I molecules. Furthermore, the CD8/¹ 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 CD8/β¹TCR-/β¹ IELs are restricted by H-2K and H-2D molecules, whereas the unusual subset of CD8/¹TCR-/β¹ resident IELs recognize nonclassical MHC class I–like molecules that are distinct from CD1.

Key Words: major histocompatibility complex • CD1 • intestinal intraepithelial lymphocytes • CD8 • gene-targeted mouse

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This article has been cited by other articles:

• Park, S.-H., Weiss, A., Benlagha, K., Kyin, T., Teyton, L., Bendelac, A. (2001). The Mouse Cd1d-Restricted Repertoire Is Dominated by a Few Autoreactive T Cell Receptor Families. JEM 193: 893-904 [Abstract] [Full Text]  
• Shinkai, K., Locksley, R. M. (2000). Cd1, Tuberculosis, and the Evolution of Major Histocompatibility Complex Molecules. JEM 191: 907-914 [Full Text]  

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