T-cell repertoire in a strain of transgenic C57BL/6 mice with theHLA-DRAgene on the X-chromosome

✍ Scribed by Yoshinori Fukui; Yukio Esaki; Akinori Kimura; Katsuiku Hirokawa; Yasuharu Nishimura; Takehiko Sasazuki

• Publisher: Springer-Verlag
• Year: 1993
• Tongue: English
• Weight: 799 KB
• Volume: 37
• Category: Article
• ISSN: 0093-7711
• DOI: 10.1007/bf00191886

✦ Synopsis

We have established a strain of transgenic mice in which the HLA-DRA gene was integrated into the Xchromosome and the xenogeneic mixed isotype molecule, DR~E/3 b, was expressed in a cell type-specific manner, although the transgenie DRA gene contained only 268 base pairs of the 5'-flanking region. The DRo~E/3 b molecules expressed in the transgenic mice functioned as major histocompatibility complex (MHC) class 1I to select T-cell repertoire, and to stimulate mixed lymphocyte reaction. In female transgenic mice homozygous for HLA-DRA (DRa-B6-F-homo) and male transgenic mice (DRa-Bt-M), DRaE~ b molecules were expressed in almost all of the MHC class II Ab-positive cells. In contrast, the expression of DRaE/3 b molecules in female transgenic mice hemizygous for HLA-DRA (DRa-B6-F-hemi) was found only in part of the A b positive cells, and the proportion of cells expressing the DRotEl3 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-Vll, which are eliminated from the peripheral repertoire in mice expressing selfsuperantigen and MHC class II E molecules, were incomplete in DRct-B6-F-hemi as compared with those in DRo~-B6-F-homo, and were correlated with the proportion of DRotE/3b-positive spleen cells. These observations suggested that the number of bone marrow-derived cells expressing DRctE~3 b molecules was critical for clonal deletions of Tcrb-V5 ÷ and Tcrb-V11 ÷ T cells in the thymus.