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Mice Lacking Terminal Deoxynucleotidyl Transferase: Adult Mice with a Fetal Antigen Receptor Repertoire
Author(s) -
GILFILLAN SUSAN,
BENOIST CHRISTOPHE,
MATHIS DIANE
Publication year - 1995
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1995.tb00099.x
Subject(s) - terminal deoxynucleotidyl transferase , biology , repertoire , t cell receptor , antigen , immune system , receptor , microbiology and biotechnology , immunology , genetics , t cell , tunel assay , apoptosis , physics , acoustics
TdT knock-out mice have established the role of this enzyme in vivo: TdT mediates the transition from the relatively limited fetal to the highly diverse adult antigen receptor repertoire by adding template independent "N" nucleotides and disrupting homology-directed recombination. Lacking this source of diversity, TdT degree mice harbor essentially fetal antigen receptor repertoires. In alpha beta TCRs, the TdT null mutation affects the length and diversity of the CDR3 loops thought to be important in "directing" MHC/peptide recognition. N- CDR3 loops appear to wield less influence than do their N+ counterparts--positive selection is more efficient in the TdT degree animals and the peripheral repertiore is more polyreactive and less peptide-oriented than is the N+ repertoire. However, this loss of specificity does not markedly diminish the response to specific peptides. Overall, mice harboring essentially fetal repertoires are robust and effectively respond to a wide variety of challenges to the immune system.