T-cell antigenic peptides from sperm whale myoglobin fold as amphipathic helices: a possible determinant for immunodominance?

Abstract

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)