1907 J. Exp. Med. The R ockefeller University Press • 0022-1007/ 99/ 06/ 1907/ 15 $2.00 Volume 189, Number 12, June 21, 1999 1907–1921 http:/ / www.jem.org An Invariant T Cell Receptor Chain Defines a Novel TAP-independent Major Histocompatibility Complex Class Ib–restricted / T Cell Subpopulation in Mammals By Florence Tilloy,* Emmanuel Treiner,* Se-Ho Park, § Corinne Garcia, ‡ François Lemonnier, Henri de la Salle, ¶ Albert Bendelac, § Marc Bonneville,** and Olivier Lantz * ‡‡ From *Institut N ational de la Santé et de la R echerche Médicale (IN SER M) U25 and ‡ INSERM U373, Hôpital N ecker, 75015 Paris, France; the § Department of Molecular Biology, Princeton University, Princeton, N ew Jersey 08540; Département SIDA -R étrovirus, Unité d’Immunité Cellulaire A ntivirale, Institut Pasteur, 75724 Paris, France; ¶ CJF-93-42, Établissement de Transfusion Sanguine, 67065 Strasbourg, France; **INSERM U463, Institut de Biologie, 44035 N antes, France; and ‡‡ University Paris X I, 94276 Le Kremlin-Bicêtre, France Summary We describe here a new subset of T cells, found in humans, mice, and cattle. These cells bear a canonical T cell receptor (TCR ) chain containing hAV7S2 and AJ33 in humans and the ho- mologous AV19-AJ33 in mice and cattle with a CDR 3 of constant length. These T cells are CD4 - CD8 - double-negative (DN) T cells in the three species and also CD8 in humans. In humans, their frequency was 1/ 10 in DN, 1/ 50 in CD8 + , and 1/ 6,000 in CD4 + lympho- cytes, and they display an activated/ memory phenotype (CD45R A lo CD45RO + ). They prefer- entially use hBV2S1 and hBV13 segments and have an oligoclonal V repertoire suggesting peripheral expansions. These cells were present in major histocompatibility complex (MHC) class II– and transporter associated with antigen processing (TAP)-deficient humans and mice and also in classical MHC class I– and CD1-deficient mice but were absent from 2-microglo- bulin–deficient mice, indicating their probable selection by a nonclassical MHC class Ib mole- cule distinct from CD1. The conservation between mammalian species, the abundance, and the unique selection pattern suggest an important role for cells using this novel canonical TCR chain. Key words: invariant T cell receptor chain • CD4 - CD8 - T cells • humans • cattle • mice B and T lymphocytes display a wide repertoire of antigen receptors, made by random recombination of V, (D), and J segments and trimming/ addition of nucleotides at the junctions between these rearranged segments (1). Besides the mainstream lymphocytes, three different types of cell sub- populations have been described that have a limited reper- toire diversity: the B1 B cell subset (2, 3), some / T cell subpopulations (4), and the TCR / + NK1 T cells (5). Restricted repertoires seem to define discrete lymphocyte subpopulations at the frontier between innate and adaptive immunity, as these selected repertoires may allow the pres- ence of a high frequency of preexisting cells reactive against phylogenetically conserved antigens (6, 7). Alternatively, cells with such a restricted repertoire may play an immuno- regulatory role or another physiologic function, such as the wound healing, that results from the secretion of keratino- cyte growth factor (8) by / dendritic epithelial cells (DECs) 1 recognizing self-ligands (9). B1 cells, which appear early during embryonic life, use recurrent VDJ combinations with few “N” additions (10), and seem to be selected by endogenous ligands (11). Simi- larly, some / T cell subsets appear early during ontogeny and use peculiar V-J combinations without N additions (12). These recurrent sequences seem to be favored by en- zymatic constraints linked to the recombination process, such as homologous region–guided recombination (4). F. Tilloy and E. Treiner contributed equally to this work. 1 A bbreviations used in this paper: APC, allophycocyanin; 2m, 2-micro- globulin; B6, C57BL/ 6; DEC, dendritic epithelial cell; DN, CD4 - CD8 - double-negative; IEL, intraepithelial lymphocyte; TAP, transporter asso- ciated with antigen processing; TC, Tricolor. on October 6, 2015 jem.rupress.org Downloaded from Published June 21, 1999