L R Lark | PubMed Health

PubMed1996

Immunotoxins: an update.

The use of immunotoxins (ITs) in the therapy of cancer, graft-vs-host disease (GvHD), autoimmune diseases, and AIDS has been ongoing for the past two decades. ITs contain a targeting moiety for delivery and a toxic moiety for cytotoxicity. Theoretically, one molecule of a toxin, routed to the appropriate cellular compartment, will be lethal to a cell. Newly developed MoAbs, toxins, and molecular biological technologies have enabled researchers to construct ITs that can effectively kill many different cell types. In fact, phase I/II clinical trials have given promising results. Although nonspecific toxicity and immunogenicity still limit the use of IT therapy, these agents hold enormous promise in an optimal setting to treat minimal disease.

Animals↗

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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)

Amino Acid Sequence↗