The imprint of intrathymic self-peptides on the mature T cell receptor repertoire

The analysis of T cell receptor α (TCRα) chains in mice transgenic for a TCRβ chain has allowed us to demonstrate a central role for self-peptides in the positive intrathymic selection of major histocompatibility complex (MHC) class II-restricted T cells. Analysis of specific Vα-Jα joins in mature CD4⁺ TCR(high) thymocytes and in peripheral CD4⁺ T cells revealed a limitation in amino-acid sequences. By analysis of immature thymocytes, we could show that this limited repertoire was selected from a more diverse repertoire. By analysis of the same β chain-transgenic mice bred to H-2Ma- deficient mice that express one or a very limited number of peptides, we could demonstrate that the Vα-Jα join repertoire was now altered and much more limited. Together, these data provide molecular and genetic evidence that the intrathymic positive selection of the TCR repertoire iS critically affected by self-peptides presented by MHC class II molecules, most likely on thymic cortical epithelial cells.