期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 39, 期 8, 页码 2136-2145出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.200939480
关键词
Animal models; Immune responses; T cells; Vaccination; VDJ recombination
类别
资金
- Agence Nationale de la Recherche contre le SIDA (ANRS)
- Association Francaise contre les Myopathies (AFM)
- FP6 European Compuvac and Clinigene
- CNRS [UMR 7211/INSERM U959, UMR 8162]
- INSERM [UMR-S 945]
- University of Ulm, Germany
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.gamma c(-/-) 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-P chain and heavy chain Ig locus. We first show that the combinatorial diversity of the TCR-P 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.gamma c(-/-) 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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