Antibody Specific for the Peptide·Major Histocompatibility Complex IS IT T CELL RECEPTOR-LIKE?

摘要: Antibodies recognizing peptide bound to a major histocompatability complex (MHC) protein usually have higher affinity for the composite peptide·MHC (pMHC) ligand than T cell receptors (TCR) with same specificity. Because solvent-accessible area constitutes only small portion of contacting pMHC surface, we hypothesized that contribution MHC moiety TCR-pMHC stability is limited, ensuring increment binding energy delivered by be distinguishable TCR or peptide-specific antibody. This suggests gain in antibody-pMHC interaction can achieved through an increase on-rate without significant change off-rate interaction. To test hypothesis, analyzed ovalbumin (pOV8) and its variants associated soluble H-2Kb 25-D1.16 monoclonal antibody compared it complexes OT-1 TCR. comparison revealed substantially In contrast, both exhibited comparably fast off-rates. Sequencing VH VL genes showed they very few somatic mutations those occur mainly framework regions. We propose above features constitute signature recognition MHC-bound antigens TCR-like antibodies, which could explain why latter are rarely produced vivo.