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

• Published in: The Journal of biological chemistry 2000-08, Vol.275 (32), p.24679-24685
• Main Authors: Moy, F J, Desai, S A, Wang, X, Noronha, E J, Zhou, Q, Ferrone, S, Powers, R
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal; Computer Graphics; Crystallography, X-Ray; histocompatibility antigen HLA; Histocompatibility Antigens Class I - chemistry; Histocompatibility Antigens Class I - immunology; Humans; Models, Molecular; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular - methods; Peptides - chemistry; Peptides - immunology; Peptides, Cyclic - chemistry; Peptides, Cyclic - immunology; Protein Conformation; Protein Structure, Secondary
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M003647200

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 β 2 -μ-associated and β 2 -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 β 2 -μ-associated and β 2 -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 X 19 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 α 3 domain. Analysis by two-dimensional transfer nuclear Overhauser effect spectroscopy of the induced solution structures of the linear X 19 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 β 2 -μ-associated HLA class I heavy chains. The structural similarity between the linear X 19 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.