J. Exp. Med., Volume 187, Number 11, June 1, 1998 1871-1883

Quantitative Analysis of the T Cell Repertoire Selected by a Single Peptide-Major Histocompatibility Complex

By Laurent Gapin,^* Yoshinori Fukui, Jean Kanellopoulos,^* Tetsuro Sano, Armanda Casrouge,^* Vanessa Malier,^* Emmanuel Beaudoing,^§ Daniel Gautheret,^§ Jean-Michel Claverie,^§ Takehiko Sasazuki, and Philippe Kourilsky^*

From the ^* Laboratoire de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale U277 and Institut Pasteur, 75724 Paris, France; the  Department of Genetics, Medical Institute of Bioregulation and Ministry of Education, Science, Sports and Culture,  Japan Science and Technology Corporation, Fukuoka 812, Japan; and the ^§ Information Genetique et Structurale, Centre National de la Recherche Scientifique, Institut de Biologie Structurale et Microbiologie, 13402 Marseille, France

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 V11-J1.1 or V12-J1.1 rearrangements. We found that a single peptide-MHC class II complex positively selects at least 10⁵ different V rearrangements. Our data yield a first evaluation of the size of the T cell repertoire. In addition, they provide evidence that the single E52-68-I-A^b 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  chain repertoire bears the imprint of the selecting self-peptide.

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