Selection and Expansion of CD8{alpha}/{alpha}1 T Cell Receptor {alpha}/{beta}1 Intestinal Intraepithelial Lymphocytes in the Absence of Both Classical Major Histocompatibility Complex Class I and Nonclassical CD1 Molecules

doi:10.1084/jem.190.6.885

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© The Rockefeller University Press, 0022-1007/1999/9/885/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 885-890

Selection and Expansion of CD8 ${alpha}$ / ${alpha}$ ¹ T Cell Receptor ${alpha}$ /ß¹ Intestinal Intraepithelial Lymphocytes in the Absence of Both Classical Major Histocompatibility Complex Class I and Nonclassical CD1 Molecules

Se-Ho Park^a, Delphine Guy-Grand^b, François A. Lemonnier^c, Chyung-Ru Wang^d, Albert Bendelac^a, and Bana Jabri^a
^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

Correspondence to: Bana Jabri, Department of Molecular Biology, Princeton University, Princeton, NJ 08544. Tel:609-258-5351 Fax:609-258-2205 E-mail:bjabri{at}molbio.princeton.edu.

Intestinal intraepithelial lymphocytes (IELs) in mice includetwo main subsets of TCR- ${alpha}$ /ß¹ cells which differ functionallyand ontogenically from each other. One expresses the CD8 ${alpha}$ / ${alpha}$ homodimer,whereas the other expresses the CD8 ${alpha}$ /ß heterodimer. Althoughthe presence of all CD8⁺TCR- ${alpha}$ /ß¹ IELs is dependent on ß2-microglobulinmolecules, the nature of the major histocompatibility complex(MHC) class I molecules recognized by the CD8 ${alpha}$ / ${alpha}$ and the CD8 ${alpha}$ /ß¹subsets has remained elusive. Using mutant mice lacking theexpression of both H2-K^b and H2-D^b, we show that the CD8 ${alpha}$ /ß¹TCR- ${alpha}$ /ß¹subset is dependent on K or D molecules, whereas the CD8 ${alpha}$ / ${alpha}$ ¹TCR- ${alpha}$ /ß¹subset is independent of classical MHC class I molecules. Furthermore,the CD8 ${alpha}$ / ${alpha}$ ¹ cells are conserved in mice lacking expression ofCD1, a nonclassical MHC class I–like molecule previouslyproposed to be a potential ligand for IELs. Using transporterassociated with antigen processing (TAP)-deficient mice, thiscell population can be further separated into a TAP-dependentand a TAP-independent subset, suggesting either the recognitionof two nonclassical MHC-like molecules, only one of which isTAP dependent, or the involvement of a single nonclassical MHC-likemolecule that is only partially TAP dependent. These findingsdemonstrate that CD8 ${alpha}$ /ß¹TCR- ${alpha}$ /ß¹ IELs are restrictedby H-2K and H-2D molecules, whereas the unusual subset of CD8 ${alpha}$ / ${alpha}$ ¹TCR- ${alpha}$ /ß¹resident IELs recognize nonclassical MHC class I–likemolecules that are distinct from CD1.

Key Words: major histocompatibility complex, CD1, intestinal intraepitheliallymphocytes, CD8, gene-targeted mouse

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Selection and Expansion of CD8/1 T Cell Receptor /ß1 Intestinal Intraepithelial Lymphocytes in the Absence of Both Classical Major Histocompatibility Complex Class I and Nonclassical CD1 Molecules

Selection and Expansion of CD8 ${alpha}$ / ${alpha}$ ¹ T Cell Receptor ${alpha}$ /ß¹ Intestinal Intraepithelial Lymphocytes in the Absence of Both Classical Major Histocompatibility Complex Class I and Nonclassical CD1 Molecules