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The Journal of Immunology, 2002, 169: 3736-3743.
Copyright © 2002 by The American Association of Immunologists

T Cell Receptor-{gamma} Allele-Specific Selection of V{gamma}1/V{delta}4 Cells in the Intestinal Epithelium1

Kalliopi Grigoriadou, Laurent Boucontet and Pablo Pereira2

Unité du Développement des Lymphocytes, Center National de la Recherche Scientifique, Unité de Recherche Associée, Institut Pasteur, Paris, France

Previous genetic analyses have shown that the relative representation of subsets of {gamma}{delta} intestinal intraepithelial lymphocytes (i-IELs) is influenced by genes linked to the TCR{gamma}, TCR{delta}, and MHC loci. Here, we have analyzed V-gene use in {gamma}{delta} i-IELs from C57BL/6 (B6) and C57BL/10 (B10) mice and from their F1 and F2 progenies with a larger panel of V{gamma}- and V{delta}-specific mAbs and have shown that the influence of TCR{gamma}-linked genes operates at two levels: one influencing the representation of V{gamma}1 (or V{gamma}7) i-IELs and other acting specifically on the V{gamma}1/V{delta}4 i-IEL subset, which represents 3% and 15% of the {gamma}{delta} i-IELs in B6 and B10 mice, respectively. Analysis of mice transgenic for a rearranged V{gamma}1J{gamma}4C{gamma}4 chain of B6 origin demonstrated that the TCR{gamma}-linked genes influencing the representation of the V{gamma}1/V{delta}4 i-IEL subset are the structural genes of TCR{gamma} chains. This influence is allele specific and cell autonomous, as evidenced by the different behavior of V{gamma}1/V{delta}4 cells bearing either parental allele in F1 mice. The representation of V{gamma}1/V{delta}4 cells among {gamma}{delta} thymocytes is similar in B6 and B10 mice, demonstrating that the V{delta}4 chain can pair well with both alleles of the V{gamma}1J{gamma}4C{gamma}4 chain and strongly suggesting that a cellular selection mechanism is responsible for the observed differences. The V{gamma}1-J{gamma}4 junctional amino acid sequences of B6 V{gamma}1/V{delta}4 i-IELs are diverse but display less variation in length than those found in similar cells from B10 mice, indicating that B6 V{gamma}1/V{delta}4 cells are the target of this cellular selection event.




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