A monoclonal antibody recognizing a new epitope on CD81 inhibits T-cell migration without inducing cytokine production.

Abstract

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.

• Authors: Takuya Hasezaki, Tadahiko Yoshima, Mikael Mattsson, Anna Särnefält, Keiko Takubo
• Journal: Journal of biochemistry (J Biochem) Vol. 167 Issue 4 Pg. 399-409 (Apr 01 2020) ISSN: 1756-2651 [Electronic] England
• PMID: 31794019 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• CD81 protein, human
• Cytokines
• Epitopes
• Tetraspanin 28

Topics

• Antibodies, Monoclonal (immunology)
• Cell Movement (immunology)
• Cell Proliferation
• Cytokines (biosynthesis, immunology)
• Epitopes (immunology)
• Humans
• Jurkat Cells
• Leukocytes, Mononuclear (cytology, immunology)
• T-Lymphocytes (immunology)
• Tetraspanin 28 (immunology, isolation & purification)