Human HLA-DQ_β chain presents minor lymphocyte stimulating locus gene products and clonally deletes TCR V_β6⁺, V_β8.1⁺ T cells in single transgenic mice

Minor lymphocyte stimulating locus (Mls) gene products in association with mouse major histocompatibility complex (MHC) class II molecules are known to determine the repertoire of T-cell receptor (TCR) in mature T cells. In order to test whether human class II molecules can present mouse Mls, HLA-DQ_β transgenic mice were generated. The expression and function of the DQ_β transgene were studied in the progeny of one selected founder which was H-2^f and H-2E negative. In these mice, DQ_β molecules pairing with mouse A_α chain and invariant chain are expressed on the cell surface in a tissue-specific manner. When the DQ_β gene was bred into the Mls-1^a strain DBA/1 (H-2^q), T cells bearing V_β6 and V_β8.1 TCR were clonally deleted in the thymus of DQ_β⁺ transgenics but not in DQ_β-negative full sibs. Thus, the data presented here clearly demonstrate that the human MHC DQ_β chain can present Mls in the clonal deletion of T cells. Our results also suggest the requirement for an interaction between CD4 and class II molecules (α chain) for clonal deletion of T cells to occur.