T-cell repertoire in a strain of transgenic C57BL/6 mice with the HLA-DRA gene on the X-chromosome.

We have established a strain of transgenic mice in which the HLA-DRA gene was integrated into the X-chromosome and the xenogeneic mixed isotype molecule, DR alpha E beta b, was expressed in a cell type-specific manner, although the transgenic DRA gene contained only 268 base pairs of the 5'-flanking region. The DR alpha E beta b molecules expressed in the transgenic mice functioned as major histocompatibility complex (MHC) class II to select T-cell repertoire, and to stimulate mixed lymphocyte reaction. In female transgenic mice homozygous for HLA-DRA (DR alpha-B6-F-homo) and male transgenic mice (DR alpha-B6-M), DR alpha E beta b molecules were expressed in almost all of the MHC class II Ab-positive cells. In contrast, the expression of DR alpha E beta b molecules in female transgenic mice hemizygous for HLA-DRA (DR alpha-B6-F-hemi) was found only in part of the Ab positive cells, and the proportion of cells expressing the DR alpha E beta b molecules varied due to random inactivation of one of the X-chromosomes. Clonal deletions of the T cells and mature thymocytes bearing Tcrb-V5 and Tcrb-V11, which are eliminated from the peripheral repertoire in mice expressing self-superantigen and MHC class II E molecules, were incomplete in DR alpha-B6-F-hemi as compared with those in DR alpha-B6-F-homo, and were correlated with the proportion of DR alpha E beta b-positive spleen cells. These observations suggested that the number of bone marrow-derived cells expressing DR alpha E beta b molecules was critical for clonal deletions of Tcrb-V5+ and Tcrb-V11+ T cells in the thymus.