NEGATIVE AND POSITIVE SELECTION BY HLA-DR3(DRW17) MOLECULES IN TRANSGENIC MICE

The establishment of HLA transgenic mice as models for autoimmune diso rders requires that the HLA molecules can be efficiently recognized an d mediate positive and negative selection of mouse T cells. This quest ion was investigated in DR3(DRw17) transgenic mice backcrossed to the B10.Q(H-2(q)) strain which does not form mixed mouse-human class II he terodimers. Here we report that efficient negative selection on DR3(DR w17) molecules was observed for v beta 5, 11, and 13 subpopulations of CD4(+)T cells, but not for v beta 4, 7, 8, 9, and 10. v beta 5 and 11 cells are also negatively selected by mouse class II E molecules whic h is the structural homologue to DR molecules. Positive selection on D R3(DRw17) was only observed for v beta 6 cells but this was less effic ient than positive selection of v beta 6 cells by E molecules. The dat a indicate that DR3(DRw17) molecules select similar subgroups of mouse T cells as E molecules although with slightly different efficiency.