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A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking

Katherine J Susa1, Tom Cm Seegar1, Stephen C Blacklow1,2

  • 1Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, United States.

Elife
|April 28, 2020
PubMed

Insights

The CD81 protein requires its ectodomain to transport CD19 to the cell surface. This interaction is dynamically regulated during B cell activation, offering new ways to control B cell function.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CD81 and CD19 are key components of the B cell co-receptor complex.
  • CD19 is part of the Ig superfamily, while CD81 belongs to the less understood tetraspanin family.
  • Tetraspanins regulate crucial cellular processes like protein trafficking.

Purpose of the Study:

  • To investigate the role of CD81's ectodomain in CD19 trafficking.
  • To characterize the binding epitope of the anti-CD81 antibody 5A6.
  • To understand the dynamic regulation of the CD81-CD19 interaction in B cell activation.

Main Methods:

  • Investigated CD81-mediated CD19 cell surface transport.
  • Analyzed the conformational epitope recognized by the anti-CD81 antibody 5A6.
  • Utilized site-directed mutagenesis to assess the impact of CD81-CD19 interface mutations on CD19 export.

Main Results:

  • CD81's ectodomain is essential for trafficking CD19 to the cell surface.
  • The anti-CD81 antibody 5A6 binds to a conformational epitope masked by CD19 binding.
  • Mutations at the CD81-CD19 interface impair CD19 export activity.
  • The CD81-CD19 interaction is dynamically regulated during B cell activation.

Conclusions:

  • The CD81-CD19 interaction is dynamically regulated upon B cell activation.
  • This dynamic regulation can be leveraged to modulate B cell function.
  • Findings enhance understanding of B cell biology and tetraspanin function.

Keywords:
B cellantibodybiochemistrychemical biologyhumantetraspanin

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