Alloreactive T-lymphocyte clones detecting epitopes uniquely expressed on HLA-D homozygous cells

Specificity analysis of two unusual alloreactive T-cell clones (TCC) is presented. In repeated in vitro sensitizations of various donors against irradiated HLA-A2, B44, DRw11, DRw52, DQw3, Dw5 homozygous stimulating cells, 202 autonomously proliferating TCC were isolated. Two of these, from different donors, responded against a majority of DRw11 homozygotes, but not against DRw11+ individuals from within or without the family of the original priming cells. Kinetic and stimulator cell titration experiments showed that the reason for this was not to be found in gene-dose effects. One out of 14 non-DRw11+ homozygotes was found that stimulated both TCC: this donor was DRw8+, Dw8+. Stimulation of the TCC was blocked by some anti-DR, and by multi-locus, monoclonal antibodies, but not by those specific for DQ or DP products. Thus, the existence of unique DR-associated stimulating determinants carried only by homozygous cells is demonstrated in man. Physiologically, this might imply that the actual restriction repertoire of HLA-DR homozygotes is not reduced to one half that of heterozygotes as expected.