| Reference | ||
|---|---|---|
| Reference Type | Literature | IEDB_Reference:1032743 |
| Title | Hydrogen/deuterium exchange mass spectrometry and computational modeling reveal a discontinuous epitope of an antibody/TL1A Interaction. | |
| Authors | Richard Y-C Huang; Stanley R Krystek Jr; Nathan Felix; Robert F Graziano; Mohan Srinivasan; Achal Pashine; Guodong Chen | |
| Affiliations | a Bioanalytical and Discovery Analytical Sciences, Pharmaceutical Candidate Optimization, Research and Development , Bristol-Myers Squibb Company , Princeton , NJ , USA; b Molecular Discovery Technologies, Research and Development , Bristol-Myers Squibb Company , Princeton , NJ , USA; c Discovery Biology, Research and Development , Bristol-Myers Squibb Company , Princeton , NJ , USA; d Biologics Discovery California, Research and Development , Bristol-Myers Squibb Company , Redwood City , CA , USA. | |
| Journal | MAbs | |
| Year | 2018 | |
| Abstract | TL1A, a tumor necrosis factor-like cytokine, is a ligand for the death domain receptor DR3. TL1A, upon binding to DR3, can stimulate lymphocytes and trigger secretion of proinflammatory cytokines. Therefore, blockade of TL1A/DR3 interaction may be a potential therapeutic strategy for autoimmune and inflammatory diseases. Recently, the anti-TL1A monoclonal antibody 1 (mAb1) with a strong potency in blocking the TL1A/DR3 interaction was identified. Here, we report on the use of hydrogen/deuterium exchange mass spectrometry (HDX-MS) to obtain molecular-level details of mAb1's binding epitope on TL1A. HDX coupled with electron-transfer dissociation MS provided residue-level epitope information. The HDX dataset, in combination with solvent accessible surface area (SASA) analysis and computational modeling, revealed a discontinuous epitope within the predicted interaction interface of TL1A and DR3. The epitope regions span a distance within the approximate size of the variable domains of mAb1's heavy and light chains, indicating it uses a unique mechanism of action to block the TL1A/DR3 interaction. | |
| Curation Last Updated | 2023-08-18 23:37:45 | |
| Epitope | ||
|---|---|---|
| Epitope ID | 2134772 | IEDB_epitope:2134772 |
| Chemical Type | Discontinuous peptide | |
| Source Name | Tumor necrosis factor ligand superfamily member 15 | |
| Source Organism | Homo sapiens (human) | |
| Discontinuous Residues | Q83, V84, Y85, A86, P87, L88, R89, A90, D91, G92, D93, K94, P95, R96, A97, H98, L99, T100, V101, V102, R103, Q104, T105, P106, T107, Q108, H109, F110, K111, N112, Q113, F114, E164, I165, R166, Q167, A168, G169, R170, P171, N172, K173, P174, D175, S176, I177, T178 | |
| Epitope Reference Details | ||
|---|---|---|
| Epitope Structure Defines | Partial Epitope | |
| Epitope Name | Epitope of mAb1 on TL1A | |
| Reference Region | Q85, V86, Y87, A88, P89, L90, R91, A92, D93, G94, D95, K96, P97, R98, A99, H100, L101, T102, V103, V104, R105, Q106, T107, P108, T109, Q110, H111, F112, K113, N114, Q115, F116, E166, I167, R168, Q169, A170, G171, R172, P173, N174, K175, P176, D177, S178, I179, T180 | |
| Location of Data in Reference | Figure 3 | |
| Immunization | ||
|---|---|---|
| Host Organism | Mus musculus (mouse) | |
| 1st In Vivo Process | ||
|---|---|---|
| In Vivo Process Type | Administration in vivo | |
| 1st Immunogen | ||
|---|---|---|
| Epitope Relation | Source Antigen | |
| Chemical Type | Protein | |
| Molecule Name | Tumor necrosis factor ligand superfamily member 15 | |
| Organism | Homo sapiens (human) | |
| Immunization Comments | ||
|---|---|---|
| Immunization Comments | The anti-hTL1A IgG4 mAb, mAb1, was developed at Bristol-Myers Squibb Company. The details of the immunization procedure were not described. | |
| B Cell Assay | ||
|---|---|---|
| Qualitative Measurement | Positive | |
| Method/Technique | surface plasmon resonance (SPR) | |
| Measurement of | off rate | |
| Assay Type Units | 1/s | |
| Measurement Details | ||
|---|---|---|
| Quantitative measurement | 0.000029 | |
| Assayed Antibody | ||
|---|---|---|
| Assayed Antibody Source Material | Purified Immunoglobulin | |
| Assayed Antibody Immunoglobulin Domain | Entire Antibody | |
| Assayed Antibody Purification Status | Monoclonal | |
| Assayed Antibody Name | mAb1 | |
| Assayed Antibody Heavy Chain Type | IgG4 | |
| Antigen | ||
|---|---|---|
| Epitope Relation | Source Antigen | |
| Chemical Type | Protein | |
| Molecule Name | Tumor necrosis factor ligand superfamily member 15 | |
| Organism | Homo sapiens (human) | |
| Assay Reference Details | ||
|---|---|---|
| Assay Comments by IEDB Curator | The affinity of epitope-specific mAb1 for binding to TL1A was determined by SPR. | |
| Location of Assay Data in Reference | Figure S2 | |