STRUCTURAL COMPLEXITY OF ANTIGENIC DETERMINANTS FOR CLASS-I MHC-RESTRICTED, HAPTEN-SPECIFIC T-CELLS - 2 QUALITATIVELY DIFFERING TYPES OF H-2K(B)-RESTRICTED TNP EPITOPES

The understanding of chemically induced allergic or autoimmune disorde rs requires a detailed structural analysis of the antigenic determinan ts produced by chemical modification of cells. Using H-2K(b)-restricte d, TNP-specific cytotoxic mouse T cells and synthetic, K(b)-associatin g TNP-peptides, we define at least two types of functionally distingui shable TNP epitopes. The first one contains TNP in position 4 of diffe rent K(b)-binding octapeptides and is detected by the majority of in v itro-induced TNP/K(b) specific CTL. This immunodominant structure coul d be imitated by oligo-glycine based ''designer peptides,'' containing only the K(b) ''anchor-residues'' and TNP-Lys in position 4. A second , qualitatively different determinant is created by TNP-Lys in positio n 7. T cells of such specificity are rare and recognize TNP only in co ntext of unique peptide sequences. In this case, designer peptides rev ealed a complex antigenic determinant comprised of TNP-7 and unmodifie d amino acids in positions 3 and 4. Chances to form a particular deter minant of this type by chemical modification are small and, thus, each clone will detect only few epitopes per cell. In contrast, the domina nt TNP-4 epitope on differing peptides results in highly repetitive de terminants. TCR specific for the rare TNP-7 structure were found to si multaneously contact TNP in position 7 and unmodified amino acids in p ositions 3 and 4. However, they may also react individually with eithe r the peptide or the hapten part of these complex determinants. This i mplies a potentially important role of such structures in the inductio n of autoimmunities: resting T cells, bearing low affinity receptors t o self peptides may be activated by peptide/hapten complexes and allow recall responses to the isolated peptide epitope of the unmodified se lf peptide.