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Soluble nonclassical HLA generated by the metalloproteinase pathway

Yuzhi Dong1, Jaroslava Lieskovska, Dmitriy Kedrin

  • 1Laboratory of Molecular Immunology, Public Health Research Institute, Newark, NJ, USA.

Human Immunology
|July 25, 2003
PubMed

Insights

Soluble nonclassical human leukocyte antigens (HLA-E, -G) and CD1 proteins were investigated for metalloproteinase (MPase) release. HLA-E and -G are released as soluble heavy chains, but CD1d is not, suggesting a lack of CD1d-specific MPase.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Soluble classical human leukocyte antigens (HLA-A, -B, -C) are generated by membrane-bound metalloproteinases (MPases).
  • The MPase pathway yields both unstable nonconformed HLA and stable peptide-bound HLA.
  • MPase cleavage of classical HLA inversely correlates with heavy chain (HC) and beta2-microglobulin (beta(2)m) stability.

Purpose of the Study:

  • To investigate whether MPases are involved in the release of soluble nonclassical HLA (HLA-E, -G) and CD1 proteins.
  • To compare the release mechanisms of HLA-E, HLA-G, and CD1d from cell surfaces.

Main Methods:

  • Utilized transfectants expressing full-length HLA and CD1 proteins.
  • Assessed the stability of surface complexes under low pH conditions.
  • Analyzed the release of soluble heavy chains (HC) into cell supernatants.

Main Results:

  • Native surface HLA-E and -G complexes, like HLA-A2, dissociated at low pH, releasing beta(2)m-free HC into supernatants.
  • Soluble beta(2)m-free HC of HLA-E and -G were readily detected, indicating MPase-mediated release.
  • CD1d complexes remained stable at low pH, and no soluble CD1d was detected, despite the presence of beta(2)m-free CD1d HC on cells.

Conclusions:

  • Nonclassical HLA-E and -G proteins are released via a MPase-dependent pathway, similar to classical HLA.
  • CD1d proteins are not released by a similar MPase mechanism, suggesting the absence or impairment of a CD1d-specific MPase.
  • The stability of native CD1d complexes does not explain the lack of soluble products.

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