The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/6/1907/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 12, June 21, 1999 1907-1921

Articles

An Invariant T Cell Receptor {alpha} Chain Defines a Novel TAP-independent Major Histocompatibility Complex Class Ib–restricted {alpha}/β T Cell Subpopulation in Mammals

Florence Tilloy*, Emmanuel Treiner*, Se-Ho Park§, Corinne Garcia{ddagger}, François Lemonnier||, Henri de la Salle, Albert Bendelac§, Marc Bonneville**, and Olivier Lantz*,{dagger}{dagger}

From * Institut National de la Santé et de la Recherche Médicale (INSERM) U25 and {ddagger} INSERM U373, Hôpital Necker, 75015 Paris, France; the § Department of Molecular Biology, Princeton University, Princeton, New Jersey 08540; || Département SIDA-Rétrovirus, Unité d'Immunité Cellulaire Antivirale, Institut Pasteur, 75724 Paris, France; CJF-93-42, Établissement de Transfusion Sanguine, 67065 Strasbourg, France; ** INSERM U463, Institut de Biologie, 44035 Nantes, France; and {dagger}{dagger} University Paris XI, 94276 Le Kremlin-Bicêtre, France

We describe here a new subset of T cells, found in humans, mice, and cattle. These cells bear a canonical T cell receptor (TCR) {alpha} chain containing hAV7S2 and AJ33 in humans and the homologous AV19-AJ33 in mice and cattle with a CDR3 of constant length. These T cells are CD4–CD8– double-negative (DN) T cells in the three species and also CD8{alpha}{alpha} in humans. In humans, their frequency was ~1/10 in DN, 1/50 in CD8{alpha}+, and 1/6,000 in CD4+ lymphocytes, and they display an activated/memory phenotype (CD45RAloCD45RO+). They preferentially use hBV2S1 and hBV13 segments and have an oligoclonal Vβ 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 β2-microglobulin–deficient mice, indicating their probable selection by a nonclassical MHC class Ib molecule 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 {alpha} chain.

Key Words: invariant T cell receptor {alpha} chain • CD4–CD8– T cells • humans • cattle • mice

Address correspondence to Oliver Lantz, Unité INSERM 25, Hôpital Necker, 155 rue de Sèvres, 75015 Paris, France. Phone: 33-1-44-49-53-75; Fax: 33-1-43-06-23-88; E-mail: lantz{at}infobiogen.fr

Isabelle Cissé is greatly thanked for managing the specific pathogen–free animal facility. We thank Delphine Guy-Grand and Nadine Cerf-Bensussan for intestinal lymphocytes, Alain Fisher's team and the patients for allowing us to obtain MHC class II–deficient patient samples, V. Braud for HLA-E tetramers, and J. Forman for anti–Qa-1 clones. J. Naessens is gratefully acknowledged for the anti–cattle lymphocyte subpopulation antibodies. I. Schwartz is thanked for her help in obtaining these antibodies and the second step reagents, and Sarah Boudali for her help in making the mouse T–T hybridomas. We thank Claude Carnaud and Polly Matzinger for discussions and for reviewing the manuscript, and Martine Bruley-Rosset and Jean-François Bach for support.

F. Tilloy and E. Treiner contributed equally to this work.

Abbreviations used: APC, allophycocyanin; β2m, β2-microglobulin; B6, C57BL/6; DEC, dendritic epithelial cell; DN, CD4–CD8– double-negative; IEL, intraepithelial lymphocyte; TAP, transporter associated with antigen processing; TC, Tricolor.


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