A monoclonal antibody recognizing a new epitope on CD81 inhibits T-cell migration without inducing cytokine production
| Autor: | Takuya Hasezaki, Keiko Takubo, Mikael Mattsson, Tadahiko Yoshima, Anna Särnefält |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Leukocyte migration
Phage display medicine.drug_class viruses medicine.medical_treatment T-Lymphocytes chemical and pharmacologic phenomena Monoclonal antibody Biochemistry Epitope Tetraspanin 28 03 medical and health sciences Epitopes Jurkat Cells 0302 clinical medicine Cell Movement medicine Single-chain variable fragment Humans Molecular Biology 030304 developmental biology Cell Proliferation 0303 health sciences Chemistry Antibodies Monoclonal Cell migration General Medicine biochemical phenomena metabolism and nutrition Molecular biology biological factors Cytokine Epitope mapping 030220 oncology & carcinogenesis Leukocytes Mononuclear Cytokines |
| Zdroj: | Journal of biochemistry. 167(4) |
| ISSN: | 1756-2651 |
| Popis: | CD81 is involved in leukocyte migration and cytokine induction. Previous work found that anti-CD81 monoclonal antibodies (mAbs) showed therapeutic potential for several immune diseases via inhibiting leukocyte migration. Although the suppression of cell migration is a promising approach for treating immune diseases, some anti-CD81 mAbs can induce cytokine production, which may exacerbate disease. To obtain new anti-human CD81 mAbs that inhibited migration in the absence of cytokine production enhancement activity, we screened a human single chain variable fragment by phage library. One of the new anti-CD81 mAbs isolated, DSP-8250, had equivalent inhibitory cell migration activity with the established anti-CD81 mAb 5A6, but it lacked cytokine induction activity. These mAbs recognized different epitopes on CD81. mAb 5A6, which had inhibitory activity on T-cell migration and increased cytokine production, bound to three residues, Ser179, Asn180 and Phe186 of CD81. In contrast, DSP-8250, which had inhibitory activity on T-cell migration but no cytokine enhancement activity, bound to four residues, His151, Ala164, Ser168 and Asn172 of CD81 as a unique epitope. These results indicate that the set of His151, Ala164, Ser168 and Asn172 forms a novel epitope that might make the application of anti-CD81 mAb therapeutically useful. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|