QA-1(B) BINDS CONSERVED CLASS-I LEADER PEPTIDES DERIVED FROM SEVERAL MAMMALIAN-SPECIES

Qa-1(b) binds a peptide (AMAPRTLLL), referred to as Qdm (for Qa-1 dete rminant modifier), derived from the signal sequence of murine class Ia molecules. This peptide binds with high affinity and accounts for alm ost all of the peptides associated with this molecule. Human histocomp atibility leukocyte antigen (HLA)-E, a homologue of Qa-1(b), binds sim ilar peptides derived from human class Ia molecules and interacts with CD94/NKG2 receptors on natural killer cells. We used surface plasmon resonance to determine the ability of Qa-1(b) to bind related ligands representing peptides derived from the leaders of class I molecules fr om several mammalian species. All of the peptides reported to bind HLA -E bound readily to Qa-1(b). In addition, peptides derived from leader segments of different mammals also bound to Qa-1(b), indicating a con servation of this ''Qdm-like'' epitope throughout mammalian evolution. We have attempted to define a minimal peptide on a polyglycine backbo ne that binds Qa-1(b). Our previous findings showed that P2 and P9 are important but not sufficient for binding to Qa-1(b). Although a minim um peptide (GMGGGGLLL) bound Qa-1(b), its interaction was relatively w eak, as were peptides sharing five or six residues with Qdm, indicatin g that multiple native residues are required for a strong interaction. This finding is consistent with the observation that this molecule pr eferentially binds this single ligand.