How a T cell receptor-like antibody recognizes major histocompatibility complex-bound peptide.
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.
Mareeva
Tatiana
T
Department of Microbiology and Immunology and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Martinez-Hackert
Erik
E
Sykulev
Yuri
Y
D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D008285:Major Histocompatibility Complex; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell