T-cell antigenic sites tend to be amphipathic structures

Abstract

We propose, on the basis of physical chemical and biological requirements for T-cell activation by antigen, that sites on a protein that can stimulate T lymphocytes will be capable of forming a stable amphipathic structure (i.e., one with separated hydrophobic and hydrophilic surfaces), displaying periodicity in hydrophobic residues. A spectral analysis of the 12 antigenic sites to which the method could be applied indicates that the amphipathic periodicity hypothesis is valid for 10 of them, generally with reliabilities that are well above 98%, with periodicities compatible with an alpha-helical structure. An 11th case manifests a different type of amphipathicity. The analyses require only a knowledge of amino acid sequence. The finding that T-cell antigenic sites show a high correlation with amphipathicity greatly simplifies the search for such sites and is potentially important for vaccine development.