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Identification of residues in CD6 which are critical for ligand binding

D L Bodian1, J E Skonier, M A Bowen

  • 1Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.

Biochemistry
|March 4, 1997
PubMed

Insights

Researchers identified key residues in CD6, a scavenger receptor cysteine rich protein superfamily member, essential for binding its ligand, activated leukocyte cell adhesion molecule (ALCAM). This finding clarifies CD6-ALCAM interactions in immune cell function.

Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • CD6 is a cell surface protein belonging to the scavenger receptor cysteine rich protein superfamily (SRCRSF).
  • The SRCRSF family's structures and functions are not well understood.
  • CD6 interacts with activated leukocyte cell adhesion molecule (ALCAM), influencing T cell maturation and function.

Purpose of the Study:

  • To identify specific amino acid residues critical for CD6-ALCAM ligand binding.
  • To investigate the structure-function relationship of the CD6 membrane proximal SRCR domain (CD6D3).

Main Methods:

  • Sequence comparison within the SRCRSF.
  • Site-directed mutagenesis of the CD6D3 domain.
  • Characterization of fifteen CD6 mutants.
  • Assessment of ligand binding and antibody binding.

Main Results:

  • Three critical CD6 residues were identified in a low sequence conservation region.
  • Mutating these residues abolished ALCAM binding.
  • Mutations did not affect binding to conformationally sensitive anti-CD6 monoclonal antibodies (mAbs).

Conclusions:

  • This study provides the first residue-level analysis of ligand binding for an SRCRSF member.
  • Specific residues in CD6 are crucial for ALCAM interaction, independent of antibody epitope binding.
  • Understanding these interactions can inform studies on T cell regulation and immune cell adhesion.

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