How a T cell receptor-like antibody recognizes major histocompatibility complex-bound peptide.

Abstract

We determined the crystal structures of the T cell receptor (TCR)-like antibody 25-D1.16 Fab fragment bound to a complex of SIINFEKL peptide from ovalbumin and the H-2K(b) molecule. Remarkably, this antibody directly "reads" the structure of the major histocompatibility complex (MHC)-bound peptide, employing the canonical diagonal binding mode utilized by most TCRs. This is in marked contrast with another TCR-like antibody, Hyb3, bound to melanoma peptide MAGE-A1 in association with HLA-A1 MHC class I. Hyb3 assumes a non-canonical orientation over its cognate peptide-MHC and appears to recognize a conformational epitope in which the MHC contribution is dominant. We conclude that TCR-like antibodies can recognize MHC-bound peptide via two different mechanisms: one is similar to that exploited by the preponderance of TCRs and the other requires a non-canonical antibody orientation over the peptide-MHC complex.

• Authors: Tatiana Mareeva, Erik Martinez-Hackert, Yuri Sykulev
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 283 Issue 43 Pg. 29053-9 (Oct 24 2008) ISSN: 0021-9258 [Print] United States
• PMID: 18703505 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes
• Immunoglobulin Fab Fragments
• Peptides
• Receptors, Antigen, T-Cell

Topics

• Crystallography, X-Ray
• Epitopes (chemistry)
• Immunoglobulin Fab Fragments (chemistry)
• Major Histocompatibility Complex
• Models, Biological
• Models, Molecular
• Molecular Conformation
• Peptides (chemistry)
• Protein Conformation
• Receptors, Antigen, T-Cell (immunology, metabolism)