Monoclonal and recombinant antibodies with T cell receptor-like reactivity.
We will explain why major histocompatibility complex (MHC) molecules presenting peptides derived from tumour-associated antigens can be recognized not only by T cell receptors (TCR), but also by soluble proteins endowed with TCR-like reactivity. To understand how an antibody can display high affinity and specificity for a particular MHC:peptide complex, we have employed X-ray crystallography to determine the structure of a recombinant antibody, Hyb3, bound to human HLA-A1 molecules presenting the peptide EADPTGHSY that is derived from the tumour-associated antigen MAGE-Al. The results indicate that although Hyb3 recgonizes its target in a TCR-like diagonal binding mode, important differences between the two types of proteins exist that are probably due to the fact that TCR are part of a molecular assembly on the surface of effector cells, while antibodies such as Hyb3 have to carry out their function as individual molecules.
Ziegler
Andreas
A
Institut für Immungenetik, Humboldt-Universität zu Berlin, Charité Campus Virchow-Klinikum, Germany.
Coulie
Pierre G
PG
Uchańska-Ziegler
Barbara
B
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D000915:Antibody Affinity; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000276:immunology; D018360:Crystallography, X-Ray; D015788:HLA-A1 Antigen / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008024:Ligands; D008285:Major Histocompatibility Complex / Q000276:immunology; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015788:HLA-A1 Antigen; D008024:Ligands; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins