Valpha and Vbeta public repertoires are highly conserved in terminal deoxynucleotidyl transferase-deficient mice.
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, Valpha-Jalpha and Vbeta-Dbeta-Jbeta rearrangements. To measure the impact of N-region diversity on public repertoires, we have characterized the alphabeta 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(o/o) mice, even for the CDR3 loops which are shorter than those found in TdT(+/+) animals. Moreover, the 10- to 20-fold decrease in alphabeta T cell diversity in TdT(o/o) mice did not prevent T cells from undergoing affinity maturation during secondary responses. A comparison of the CDR3beta in published public and private repertoires indicates significantly reduced N-region diversity in public CDR3beta. 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 MHCalpha helices are involved in the selection of public repertoires.
Fazilleau
Nicolas
N
Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 277, Institut Pasteur, Paris, France.
Cabaniols
Jean-Pierre
JP
Lemaître
Fabrice
F
Motta
Iris
I
Kourilsky
Philippe
P
Kanellopoulos
Jean M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D022801:Complementarity Determining Regions; D004253:DNA Nucleotidylexotransferase / Q000172:deficiency*; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology
D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D004253:DNA Nucleotidylexotransferase