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, DRalphaEbeta(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 DRalphaEbeta(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 (DRalpha-B6-F-homo) and male transgenic mice (DRalpha-B6-M), DRalphaEbeta(b) molecules were expressed in almost all of the MHC class II Ab-positive cells. In contrast, the expression of DRalphaEbeta(b) molecules in female transgenic mice hemizygous for HLA-DRA (DRalpha-B6-F-hemi) was found only in part of the A(b) positive cells, and the proportion of cells expressing the DRalphaEbeta(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 DRalpha-B6-F-hemi as compared with those in DRalpha-B6-F-homo, and were correlated with the proportion of DRalphaEbeta(b)-positive spleen cells. These observations suggested that the number of bone marrow-derived cells expressing DRalphaEbeta(b) molecules was critical for clonal deletions of Tcrb-V5+ and Tcrb-V11+ T cells in the thymus.