Aromatic side-chain interactions as the origin of immunological diversity in the TyrTyrGluGlu and TyrGluTyrGlu epitopes: NMR and fluorescence evidence.
Spectroscopic methods have been applied to elucidate conformational differences responsible for the immunological diversity of two synthetic multichain copolymers, Tyr1Tyr2Glu3Glu4-poly-DL-Ala--poly-Lys and Tyr1Glu2Tyr3Glu4-poly-DL-Ala--poly-Lys. Despite their far-reaching structural similarity in the epitope peptide and complete identity in the poly-Ala--poly-Lys carrier, these two copolymers manifest a wide range of opposed immunological attributes. Different genetic control mechanisms govern their immunogenic properties, and their interactions with antigen presenting cells or T cells and B cells are mediated via different immunological routes. Following previous photoCIDNP (photoChemically Induced Dynamic Nuclear Polarization) investigations, we applied NMR and fluorescence measurements to these two copolymers in order to search for structural differences that could account for their opposed immunological behaviour. The differences between the two antigens are traced to the spatial orientation of the tyrosine residues. Hydrophobic Tyr1--Tyr3 intramolecular inter-side-chain interactions characterize the Tyr1Glu2Tyr3Glu4 polymer, whereas Tyr1 and Tyr2 in the Tyr1Tyr2Glu3Glu4 polymer are non-interacting and freely rotating. It is thus inferred that Tyr1 and Tyr2 are distant and point to different directions in space, whereas Tyr1 and Tyr3 are in close proximity, as was suggested by a previous CIDNP study and by molecular structure computations. We infer that these structural differences may relate to the different immunological behaviour of the TyrTyrGluGlu and TyrGluTyrGlu polymers.
Muszkat
K A
KA
Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Schechter
B
B
Sela
M
M
D000595:Amino Acid Sequence; D000939:Epitopes / Q000737:chemistry; D007120:Immunochemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011107:Polylysine / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence
D000939:Epitopes; D009842:Oligopeptides; D010455:Peptides; D011107:Polylysine; C019529:polyalanine; C076625:tyrosyl-tyrosyl-glutamyl-glutamic acid; C076626:tyrosyl-glutamyl-tyrosyl-glutamic acid