Robert Powers

Analysis by NMR Spectroscopy of the Structural Homology between the Linear and the Cyclic Peptide Recognized by Anti-human Leukocyte Antigen Class I Monoclonal Antibody TP25.99*

The anti-human leukocyte antigen (HLA) class I monoclonal antibody (mAb) TP25.99 has a unique specificity since it recognizes both a conformational and a linear determinant expressed on the β2-μ-associated and β2-μ-free HLA class I heavy chains, respectively. Previously, we reported the identification of a cyclic and a linear peptide that inhibits mAb TP25.99 binding to the β2-μ-associated and β2-μ-free HLA class I heavy chains (S. A. Desai, X. Wang, E. J. Noronha, Q. Zhou, V. Rebmann, H. Grosse-Wilde, F. J. Moy, R. Powers, and S. Ferrone, submitted for publication). The linear X19 and cyclic LX-8 peptides contain sequence homologous to residues 239–242, 245, and 246 and to residues 194–198, respectively, of HLA class I heavy chain α3 domain. Analysis by two-dimensional transfer nuclear Overhauser effect spectroscopy of the induced solution structures of the linear X19 and cyclic LX-8 peptides in the presence of mAb TP25.99 showed that the two peptides adopt a similar structural motif despite the lack of sequence homology. The backbone fold is suggestive of a short helical segment followed by a tight turn, reminiscent of the determinant loop region (residues 194–198) on β2-μ-associated HLA class I heavy chains. The structural similarity between the linear X19 and cyclic LX-8 peptides and the lack of sequence homology suggests that mAb TP25.99 predominantly recognizes a structural motif instead of a consensus sequence.