The mode of ligand recognition by two peptide:MHC class I-specific monoclonal antibodies.
The Ig superfamily members TCR and B cell receptor (BCR) share high structural and amino acid homology, yet interact with Ags in a distinct manner. The overall shape of the TCR ligand is rather constant, with the variation coming from the MHC polymorphism and the peptide heterogeneity. Consequently, the TCR alpha- and beta-chains form a relatively flat ligand-binding site that interacts with the peptide:MHC (pep:MHC) ligand in a fixed diagonal orientation relative to the MHC alpha-helices, with the alpha- and beta-chains of the TCR contacting the N and C termini of the pep:MHC complex, respectively. By contrast, the shape of BCR ligands varies dramatically, and the BCR exhibits much greater variability of the Ag-binding site. The mAbs 25-D1.16 (D1) and 22-C5.9 (C5), specific for the OVA-8:H-2Kb complex, allowed us to directly compare how TCR and BCR approach the same ligand. To that effect, we mapped D1 and C5 footprints over the OVA-8:H-2Kb complex. Using peptide variants and mutant MHC molecules, we show that the D1 and C5 contacts with the OVA-8:Kb complex C terminus overlap with the TCR beta-chain footprint, but that this footprint also extends to the regions of the molecule not contacted by the TCR. These studies suggest that D1 and C5 exhibit a hybrid mode of pep:MHC recognition, in part similar to that of the TCR beta-chain and in part similar to the conventional anti-MHC Ab.
Messaoudi
I
I
Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
LeMaoult
J
J
Nikolić-Zugić
J
J
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D000918:Antibody Specificity; D001120:Arginine / Q000737:chemistry; D002460:Cell Line; D017124:Conserved Sequence; D004527:Egg Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D006183:H-2 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D012997:Solvents
D000911:Antibodies, Monoclonal; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007143:Immunoglobulin Heavy Chains; D008024:Ligands; C110366:OVA-8; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012997:Solvents; D010047:Ovalbumin; D001120:Arginine