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Cutting Edge: Recombinase-Activating Gene Expression and V(D)J Recombination in CD4⁺CD3^low Mature T Lymphocytes¹

Erica Lantelme^*, Belinda Palermo^*, Luisa Granziero^*, Stefania Mantovani^*, Rita Campanelli^*, Virginia Monafo, Antonio Lanzavecchia and Claudia Giachino^2,*,§

^* S. Maugeri Foundation, Instituto di Ricovero e Cura a Carottere Scientifico (IRCCS) Pavia, Italy; Department of Pediatric Sciences, University of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy; Basel Institute for Immunology, Basel, Switzerland; and ^§ Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

The recombinase-activating genes, RAG-1 and RAG-2, can be expressed by a subset of B cells within germinal centers, where they mediate secondary V(D)J rearrangements. This receptor revision mechanism could serve either receptor diversification or tolerance-induced functions. Alternatively, it might rescue those cells the receptors of which have been damaged by somatic mutation. Less is known about the occurrence of similar mechanisms in T cells. Here we show that mature T cells with defective TCR surface expression can express RAG genes and are capable of initiating secondary V(D)J rearrangements. The possibility that a cell rescue mechanism based on the generation of a novel Ag receptor might be active in peripheral T cells is envisaged.