High diversity of the immune repertoire in humanized NOD.SCID.gamma c-/- mice.
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.gammac(-/-) 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-beta chain and heavy chain Ig locus. We first show that the combinatorial diversity of the TCR-beta 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.gammac(-/-) 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.
Marodon
Gilles
G
Université Pierre et Marie Curie - Paris 6, Centre National de la Recherche Scientifique UMR 7211, Paris, France. gilles.marodon@upmc.fr
Desjardins
Delphine
D
Mercey
Laetitia
L
Baillou
Claude
C
Parent
Pierric
P
Manuel
Manuarii
M
Caux
Christophe
C
Bellier
Bertrand
B
Pasqual
Nicolas
N
Klatzmann
David
D
D000818:Animals; D000831:Animals, Newborn; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization / Q000379:methods; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D007143:Immunoglobulin Heavy Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017493:Leukocyte Common Antigens