beta-amino acid scan of a class I major histocompatibility complex-restricted alloreactive T-cell epitope

An HLA-B27-restricted self-octapeptide known to react with an alloreactive T-cell receptor has been modified by systematic substitution of a p-amino a cid for the natural cy-amino acid residue, over the whole length of the par ent epitope, All modified peptides were shown to bind to recombinant HLA-B* 2705 and induce stable major histocompatibility complex-peptide complexes, but with some variation depending on the position of the beta -amino acid o n the peptide sequence, Alteration of the natural peptide sequence at the t wo N-terminal positions (positions 1 and 2) decreases binding affinity and thermodynamic stability of the refolded complex, but all other positions (f rom position 3 to the C-terminal residue) were insensitive to the beta -ami no acid substitution. All modified peptides were recognized by an alloreact ive T-cell clone specific for the parent epitope with decreased efficiency, to an extent dependent of the position that was modified. Furthermore, the introduction of a single beta -amino acid at the first two positions of th e modified peptide was shown to be sufficient to protect them against enzym atic cleavage. Thus, beta -amino acids represent new interesting templates for alteration of T-cell epitopes to design either synthetic vaccines of T- cell receptor antagonists.