HUMAN HLA-DQ-BETA CHAIN PRESENTS MINOR LYMPHOCYTE STIMULATING LOCUS GENE-PRODUCTS AND CLONALLY DELETES TCR V-BETA-6+, V-BETA-8.1+ T-CELLS IN SINGLE TRANSGENIC MICE

Minor lymphocyte stimulating locus (Mls) gene products is 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-beta transgenic mice were generated. The expression and function of the DQ-beta transgene were studied in the progeny of one selected founder which was H-2f and H-2E negative. In these mice, DQ-beta molecules pairing with mouse A-alpha chain and invariant chain are expressed on the cell surface in a tissue-specific manner. When the DQ-beta gene was bred into the Mls-1a strain DBA/1 (H-2q), T cells bearing V-beta-6 and V-beta-8.1 TCR were clonally deleted in the thymus of DQ-beta+ transgenics but not in DQ-beta-negative full sibs. Thus, the data presented here clearly demonstrate that the human MHC DQ-beta 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 (alpha chain) for clonal deletion of T cells to occur.