| Title | Antibody specific for the peptide.major histocompatibility complex. Is it T cell receptor-like? | | Author(s) | Mareeva T, Lebedeva T, Anikeeva N, Manser T, Sykulev Y | | Institution | Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. | | Source | J Biol Chem 2004 Oct 22; 279(43):44243-9. | | MeSH | Amino Acid Sequence
Animals
Antibodies
Antibodies, Monoclonal
Antibody Specificity
Base Sequence
Biosensing Techniques
Cloning, Molecular
DNA
Edetic Acid
Hybridomas
Immunoglobulin Fragments
Kinetics
Major Histocompatibility Complex
Mice
Molecular Sequence Data
Mutation
Ovalbumin
Peptides
Plasmids
Protein Binding
Protein Structure, Tertiary
Receptors, Antigen, T-Cell
Thermodynamics
Time Factors
Transfection
| | Abstract | Antibodies recognizing peptide bound to a major histocompatibility complex (MHC) protein usually have a higher affinity for the composite peptide.MHC (pMHC) ligand than T cell receptors (TCR) with the same specificity. Because the solvent-accessible peptide area constitutes only a small portion of the contacting pMHC surface, we hypothesized that the contribution of the MHC moiety to the TCR-pMHC complex stability is limited, ensuring a small increment of the binding energy delivered by the peptide to be distinguishable by the TCR or the peptide-specific antibody. This suggests that the gain in affinity of the antibody-pMHC interaction can be achieved through an increase in the on-rate without a significant change in the off-rate of the interaction. To test the hypothesis, we have analyzed the binding of an ovalbumin peptide (pOV8) and its variants associated with soluble H-2Kb protein to the 25-D1.16 monoclonal antibody and compared it with the binding of the same pMHC complexes to the OT-1 TCR. This comparison revealed a substantially higher on-rate of the antibody-pMHC interaction compared with the TCR-pMHC interaction. In contrast, both the antibody and the TCR-pMHC complexes exhibited comparably fast off-rates. Sequencing of the 25-D1.16 VH and VL genes showed that they have very few somatic mutations and those occur mainly in framework regions. We propose that the above features constitute a signature of the recognition of MHC-bound peptide antigens by TCR and TCR-like antibodies, which could explain why the latter are rarely produced in vivo. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, U.S. Gov't, P.H.S.
| | PubMed ID | 15302863 |
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