Molecular mapping of a histocompatibility-restricted immunodominant T cell epitope with synthetic and natural peptides: implications for T cell antigenic structure.

TLDR

The periodic arrangement of key residues suggests that folding into an amphipathic α‑helix is essential for antigenicity, potentially forming hydrophilic and hydrophobic sites that interact with T‑cell receptors and antigen presentation machinery. Synthetic and natural peptides mapped the major antigenic site of myoglobin to residues 136–146, with Glu136, Lys140, and Lys145 essential for T‑cell activation, while Lys133 and Tyr146 enhance potency but are not required.

Abstract

We have prepared synthetic and natural peptides that have allowed delineation of a major antigenic site of myoglobin recognized by histocompatibility (I-Ed)-restricted T cell clones. The smallest peptide capable of stimulating T cell proliferation consisted of residues 136-146. Residues Glu 136, Lys 140, and Lys 145 were essential for antigenicity, whereas Lys 133 and Tyr 146 added potency but were not required for antigenicity. The periodicity of these residues suggests that folding the peptide into its native alpha-helical structure may be essential for antigenicity either by forming a hydrophilic binding site for the T cell receptor or by participating in antigen presentation. The same folding could also produce a hydrophobic site on the opposite side of the alpha-helix that could participate in hydrophobic interactions. The extrapolation of these findings to other known peptide antigens suggests that this tendency to form an amphipathic alpha-helix may be a general property of antigenic sites recognized by T cells, perhaps due to a different functional role of each type of site in eliciting T cell responses.