Structural complexity of antigenic determinants for class I MHC-restricted, hapten-specific T cells. Two qualitatively differing types of H-2Kb-restricted TNP epitopes.
The understanding of chemically induced allergic or autoimmune disorders requires a detailed structural analysis of the antigenic determinants produced by chemical modification of cells. Using H-2Kb-restricted, TNP-specific cytotoxic mouse T cells and synthetic, Kb-associating TNP-peptides, we define at least two types of functionally distinguishable TNP epitopes. The first one contains TNP in position 4 of different Kb-binding octapeptides and is detected by the majority of in vitro-induced TNP/Kb-specific CTL. This immunodominant structure could be imitated by oligo-glycine based "designer peptides," containing only the Kb "anchor-residues" and TNP-Lys in position 4. A second, qualitatively different determinant is created by TNP-Lys in position 7. T cells of such specificity are rare and recognize TNP only in context of unique peptide sequences. In this case, designer peptides revealed a complex antigenic determinant comprised of TNP-7 and unmodified amino acids in positions 3 and 4. Chances to form a particular determinant of this type by chemical modification are small and, thus, each clone will detect only few epitopes per cell. In contrast, the dominant TNP-4 epitope on differing peptides results in highly repetitive determinants. TCR specific for the rare TNP-7 structure were found to simultaneously contact TNP in position 7 and unmodified amino acids in positions 3 and 4. However, they may also react individually with either the peptide or the hapten part of these complex determinants. This implies a potentially important role of such structures in the induction of autoimmunities: resting T cells, bearing low affinity receptors to self peptides may be activated by peptide/hapten complexes and allow recall responses to the isolated peptide epitope of the unmodified self peptide.
Martin
S
S
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
von Bonin
A
A
Fessler
C
C
Pflugfelder
U
U
Weltzien
H U
HU
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D006183:H-2 Antigens / Q000502:physiology*; D006241:Haptens / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology*
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D006241:Haptens; D009842:Oligopeptides; D014301:Trinitrobenzenes