A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes

Peptides that are antigenic for T lymphocytes are ligands for two
receptors, the class I or II glycoproteins that are encoded by
genes in the major histocompatibility complex, and the idiotypic /
chain T-cell antigen receptor1–9. That a peptide must bind to an
MHC molecule to interact with a T-cell antigen receptor is the
molecular basis of the MHC restriction of antigen-recognition by T
lymphocytes10,11. In such a trimolecular interaction the amino-acid
sequence of the peptide must specify the contact with both
receptors: agretope residues bind to the MHC receptor and epitope
residues bind to the T-cell antigen receptor12,13. From a
compilation of known antigenic peptides, two algorithms have been
proposed to predict antigenic sites in proteins. One algorithm uses
linear motifs in the sequence14, whereas the other considers
peptide conformation and predicts antigenicity for amphipathic
-helices15,16. We report here that a systematic delimitation of an
antigenic site precisely identifies a predicted pentapeptide motif
as the minimal antigenic determinant presented by a class I MHC
molecule and recognized by a cytolytic T lymphocyte clone.