CARRIER-INDEPENDENT HAPTEN RECOGNITION AND PROMISCUOUS MHC RESTRICTION BY CD4 T-CELLS INDUCED BY TRINITROPHENYLATED PEPTIDES

The elucidation of mechanisms underlying the recognition of haptens by class II MHC-restricted T cells is instrumental for the understanding of chemical- and drug-induced allergies. We have previously demonstra ted that trinitrophenyl (TNP) peptides represent dominant antigenic ep itopes for CD8(+) and CD4(+) mouse T cells triggered by chemically TNP -modified APC, Here, we report the characterization of TNP-specific, C D4(+) mouse T cell lines and hybridomas that were induced in vivo and in vitro by defined hapten-conjugated peptides, These peptides, which we had previously shown to induce contact sensitivity to picryl chlori de in vivo regardless of sequence homologies to mouse proteins, were f ound to activate carrier-independent TNP-specific T cells in vitro. We interpret these findings to support our view that carrier-independent T cells, reactive to particularly repetitive hapten epitopes, may pla y a crucial role in allergies to chemicals and drugs. In addition to c arrier independence, one of our hybridomas (IT-H6/A11) exhibited a str iking promiscuity of MHC restriction, Although absolutely dependent in its TNP reactivity on the presence of MHC class II molecules, the IT H6/A11 hybridoma completely ignored class II polymorphism and even rea cted to TNP peptides presented on human DR molecules, Regarding hapten allergies in humans with a heterozygous situation for three types of class II molecules (DR, DP, and DO), such promiscuous MHC restriction should lead to the presentation of even higher epitope densities to th e respective T cell clones, Hybridoma IT-H6/A11, reacting to TNP indep endent of carrier peptide and of MHC haplotype, also allowed for an un usually systematic study of the minimal requirements for TNP recogniti on, Despite an almost complete ignorance of amino acid side chains on the carrier peptide, our data indicate a clearly position-specific int eraction of hapten and TCR.