T-cell antigenic peptides from sperm whale myoglobin fold as amphipathic helices: a possible determinant for immunodominance?
Little is known about the requirements for immunodominance in a T-cell immune response. It has been speculated that after a foreign protein has undergone proteolytic processing, resulting peptides that can take on structures favorable for binding to histocompatibility proteins and for recognition by the T-cell receptor are immunodominant. DeLisi and Berzofsky (25) have proposed that the ability of a peptide fragment to fold as an amphipathic alpha-helix may increase the likelihood of its immunodominance. In an effort to understand how structure and immunodominance might be correlated, we have studied the biophysical properties of a series of peptides from sperm whale myoglobin (SWMb) which have already been characterized with respect to activation of T-cell clones from mice immunized against the whole protein. Our results suggest that peptides corresponding to immunodominant T-cell antigenic sites from SWMb tend to fold as amphipathic alpha-helices in structure-promoting and interfacial environments. Peptides with the sequences 132-146 and 102-118 were chosen for the study because they were found to be immunodominant for myoglobin-specific T cells (8) and were predicted to form amphipathic alpha-helices based on their residue distribution. Likewise, peptides with the sequences 93-102 and 115-130, which were predicted not to favor this conformation, were used as controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Lark
L R
LR
University of Texas, Southwestern Medical Center, Dallas 75235-9041.
Berzofsky
J A
JA
Gierasch
L M
LM
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002942:Circular Dichroism; D007202:Indicators and Reagents; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000737:chemistry* / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D014907:Whales
D007202:Indicators and Reagents; D009211:Myoglobin; D010455:Peptides