Degeneracy and additional alloreactivity of drug-specific human alpha beta(+) T cell clones

It has been well established that T cells can recognize small mol. wt compo unds such as drugs. Results from previous studies revealing a high heteroge neity and cross-reactivity of drug-specific T cell clones (TCC) in individu al patients prompted us to analyze the degeneracy of drug-reactive TCR in d etail. Hence, we analyzed the MHC restriction pattern of a panel of 100 dru g-specific TCC isolated from different drug-allergic donors. We found that 28 of the tested clones showed an MHC allelle-unrestricted drug recognition . Most of these clones were at the same time highly drug specific, Le. they could only be stimulated by the original drug and not by any drug derivati ves. In contrast, TCC with the ability to interact with different drug deri vatives displayed a clearly MHC allele-restricted drug recognition. Therefo re, we concluded that the TCR of these clones is mainly interacting with si de chains of the appropriate drug molecules and hence able to tolerate alte rations in the MHC molecule. Moreover, we tested all clones for additional alloreactivity and found that 27 clones could be stimulated by a self-MHC-p eptide-drug complex as well as by a non-self-MHC-peptide complex. This cros s-reactivity with allogeneic MHC molecules was substantially higher in drug -specific TCC compared to tetanus toxoid-specific clones from the same dono rs. This suggests that from the point of view of drug-specific TCR, non-sel f-MHC-peptide complexes have a higher incidence to mimic the 'original' sel f-MHC-peptide-drug complex and this may occur for TCR recognizing self-MHC- pathogen-derived peptide complexes. Finally, the biological functions of bi specific TCC were not influenced by the nature of the stimulating ligand. B oth drug as well as allogeneic stimulation led to similar reaction patterns in the analyzed TCC.