DNA LEVEL STUDY OF ALLOREACTIVE T-CELL CLONE TARGETS

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Using restriction fragment length polymorphism analysis (RFLP), three allelic DQ-alpha and three allelic DQ-beta patterns associated DQw1 have been recognized. One of these alpha/beta pairs was found to associate with DR1, two with DR2, and a fourth with DRw6. "Complementary" alloreactive T-cell clones were generated that were able to specifically recognize one or the other of the two DR2 associated, DQw1-positive molecules of the stimulator cells. These molecules carry the same alpha chain but a different (allelic) form of beta chain. In the last few months, evidence has also been obtained by nucleotide sequencing that there are as many allelic forms of DQ-alpha and DQ-beta genes as there are different molecular DQ-alpha and DQ-beta (RFLP) patterns, and each alpha/beta gene combination is associated with the same DR allele as its corresponding molecular alpha/beta pattern pair. It would now be certainly interesting to definitively prove that: a) antibodies may recognize determinants present only on the alpha or on the beta chain of the DQ molecule, while T-cells recognize simultaneously alpha and beta determinants. An allelic modification on only one chain is sufficient to completely abrogate the T-cell alloreaction, but may not interfere with the ability of the antibodies to recognize other epitopes or epitopes of the other chain; b) specificities, against which reagents in general cannot be found because of the strong association of certain alpha with certain beta genes, can be artificially generated by co-transfecting alpha and beta genes in anusual associations; c) specific reagents (monoclonal antibodies as well as T-cell clones) can be generated against these "new" specificities. The spontaneous generation of these "new" specificities may rarely take place by transcomplementation in the presence of particular haplotype combinations. This may be the cause of the immunological failure or the immunological auto-aggression which has generally been found present in the majority of HLA associated diseases. The reagents generated against the artificially obtained "new" specificities would be useful for the early recognition of their presence at the surface of the patient cells.