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and V
Public Repertoires Are Highly Conserved in Terminal Deoxynucleotidyl Transferase-Deficient Mice1
* Unité de Biologie Moléculaire du Gène-Institut National de la Santé Et de la Recherche Médicale (INSERM) Unité 277-Institut Pasteur, Paris, France;
Cellectis, Romainville, France; and
Laboratoire d’Activation Cellulaire et Transduction des Signaux, Institut de Biochimie et de, Biophysique Moléculaire et Cellulaire, Unité Mixte de Recherche (UMR) 8619 Centre National de la Recherche Scientifique (CNRS), Université Paris Sud, Orsay, France
T cell repertoires observed in response to immunodominant and subdominant peptides include private, i.e., specific for each individual, as well as public, i.e., common to all mice or humans of the same MHC haplotype, V
-J and V
-D-J rearrangements. To measure the impact of N-region diversity on public repertoires, we have characterized the TCRs specific for several CD4 or CD8 epitopes of wild-type mice and of mice deficient in the enzyme TdT. We find that V, (D), J usage identified in public repertoires is strikingly conserved in TdT°/° mice, even for the CDR3 loops which are shorter than those found in TdT+/+ animals. Moreover, the 10- to 20-fold decrease in T cell diversity in TdT°/° mice did not prevent T cells from undergoing affinity maturation during secondary responses. A comparison of the CDR3 in published public and private repertoires indicates significantly reduced N-region diversity in public CDR3. We interpret our findings as suggesting that public repertoires are produced more efficiently than private ones by the recombination machinery. Alternatively, selection may be biased in favor of public repertoires in the context of the interactions between TCR and MHC peptide complexes and we hypothesize that MHC helices are involved in the selection of public repertoires.
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