High diversity of the immune repertoire in humanized NOD.SCID.γc−/− mice |
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Authors: | Gilles Marodon Delphine Desjardins Laetitia Mercey Claude Baillou Pierric Parent Manuarii Manuel Christophe Caux Bertrand Bellier Nicolas Pasqual David Klatzmann |
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Institution: | 1. Université Pierre et Marie Curie?‐?Paris 6;2. Centre National de la Recherche Scientifique UMR 7211, Paris, France;3. Institut National de la Santé et de la Recherche Médicale U959, H?pital de la Pitié Salpêtrière, Paris, France;4. ImmunID Technologies, CEA/iRTSV, Grenoble, France;5. INSERM U590, Centre Léon Bérard, Université Lyon, Lyon, France |
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Abstract: | The diversity of the human immune repertoire and how it relates to a functional immune response has not yet been studied in detail in humanized NOD.SCID.γc?/? immunodeficient mice. Here, we used a multiplex PCR on genomic DNA to quantify the combinatorial diversity of all possible V–J rearrangements at the TCR‐β chain and heavy chain Ig locus. We first show that the combinatorial diversity of the TCR‐β chain generated in the thymus was well preserved in the periphery, suggesting that human T cells were not vastly activated in mice, in agreement with phenotypic studies. We then show that the combinatorial diversity in NOD.SCID.γc?/? mice reached 100% of human reference samples for both the TCR and the heavy chain of Ig. To document the functionality of this repertoire, we show that a detectable but weak HLA‐restricted cellular immune response could be elicited in reconstituted mice after immunization with an adenoviral vector expressing HCV envelope glycoproteins. Altogether, our results suggest that humanized mice express a diversified repertoire and are able to mount antigen‐specific immune responses. |
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Keywords: | Animal models Immune responses T cells Vaccination VDJ recombination |
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