Use of flanking sequences to study secondary structure-activity correlations of a Mycobacterium leprae T cell epitope.
The 65-kDa protein of the intracellular pathogen M. leprae is prominent in the immune response to this mycobacterium, and individual T cell epitopes from this protein sequence have been defined. We have tested the stimulatory activity of extended analogs of the minimal peptide representing one such epitope, LQAAPALDKL, with a variety of tetrapeptide extensions added to enhance or destabilize alpha helix formation. The conformational potential of the peptides was measured by circular dichroism using aqueous trifluoroethanol as a secondary structure inducer. Although analogs with high helical potential activated T cells at low concentrations, a less helical variant was similarly potent. Activity also did not correlate with predicted overall alpha helical amphipathicity. One analog was found which stimulated T cell proliferation in the 50 pM range. The effect of tetrapeptide extensions on epitope activity is not consistent with the importance in activity of only a single stable secondary structure such as an alpha helix.
Department of Pathobiology, University of Washington, Seattle.
D C
DC
Anderson
W C
WC
Van Schooten
M E
ME
Barry
A A
AA
Janson
R R
RR
DeVries
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D002942:Circular Dichroism; D002999:Clone Cells; D000939:Epitopes; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000276:immunology*; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D000939:Epitopes; D009842:Oligopeptides