Quantitative analysis of the T cell repertoire selected by a single peptide-major histocompatibility complex.
The positive selection of CD4+ T cells requires the expression of major histocompatibility complex (MHC) class II molecules in the thymus, but the role of self-peptides complexed to class II molecules is still a matter of debate. Recently, it was observed that transgenic mice expressing a single peptide-MHC class II complex positively select significant numbers of diverse CD4+ T cells in the thymus. However, the number of selected T cell specificities has not been evaluated so far. Here, we have sequenced 700 junctional complementarity determining regions 3 (CDR3) from T cell receptors (TCRs) carrying Vbeta11-Jbeta1.1 or Vbeta12-Jbeta1.1 rearrangements. We found that a single peptide-MHC class II complex positively selects at least 10(5) different Vbeta rearrangements. Our data yield a first evaluation of the size of the T cell repertoire. In addition, they provide evidence that the single Ealpha52-68-I-Ab complex skews the amino acid frequency in the TCR CDR3 loop of positively selected T cells. A detailed analysis of CDR3 sequences indicates that a fraction of the beta chain repertoire bears the imprint of the selecting self-peptide.
Gapin
L
L
Laboratoire de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale U277 and Institut Pasteur, 75724 Paris, France.
Fukui
Y
Y
Kanellopoulos
J
J
Sano
T
T
Casrouge
A
A
Malier
V
V
Beaudoing
E
E
Gautheret
D
D
Claverie
J M
JM
Sasazuki
T
T
Kourilsky
P
P
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta