Biased TCR gene usage in alloreactive T cells specific for a structurally dissimilar MHC alloantigen

Two models of allorecognition of MHC molecules have been proposed. One emphasizes specificity for MHC molecule-bound peptides and the other for exposed MHC polymorphisms. We predicted that the latter model would predominate in responder:stimulator combinations whose MHC molecules differed extensively in their TCR-contacting surfaces and that this would be reflected in biased TCR usage. Two panels of anti-DR11 T cell clones were generated, one from a DR17 and the other from a DR15 responder. The TCR-contacting surfaces of DR17 and DR11 have multiple differences, and those of DR15 and DR11 are very similar. TCR analysis by polymerase chain reaction amplification and mAb staining revealed that five out of nine DR17 anti-DR11 clones used the V beta 13 and two the V beta 6, family. In contrast seven different V beta families were used by the eight DR15 anti-DR11 clones. A similar bias in TCR V beta usage was observed in the polyclonal DR17 and DR11 T cell lines from which the clones were derived, and in a second DR17 anti-DR11 line from a different individual. These results support the concept that specificity for the foreign MHC structure itself may play an important role in the alloresponse between responders and stimulators with structurally dissimilar MHC molecules.