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Dramatic Influence of Vß Gene Polymorphism on an Antigen-Specific CD8⁺ T Cell Response In Vivo

Hélène Bour^*, Olivier Michielin, Philippe Bousso, Jean-Charles Cerottini^* and H. Robson MacDonald^1,*

^* Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; Le Bel Institute, Louis Pasteur University, Strasbourg, France; and Laboratory of Molecular Biology of the Gene, Pasteur Institute, Institut National de la Santé et de la Recherche Médicale U277, Paris, France

According to recent crystallographic studies, the TCR-ß contacts MHC class I-bound antigenic peptides via the polymorphic V gene-encoded complementarity-determining region 1ß (CDR1ß) and the hypervariable (D)J-encoded CDR3ß and CDR3 domains. To evaluate directly the relative importance of CDR1ß polymorphism on the fine specificity of T cell responses in vivo, we have taken advantage of congenic Vß^a and Vß^b mouse strains that differ by a CDR1 polymorphism in the Vß10 gene segment. The Vß10-restricted CD8⁺ T cell response to a defined immunodominant epitope was dramatically reduced in Vß^a compared with Vß^b mice, as measured either by the expansion of Vß10⁺ cells or by the binding of MHC-peptide tetramers. These data indicate that Vß polymorphism has an important impact on TCR-ligand binding in vivo, presumably by modifying the affinity of CDR1ß-peptide interactions.

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