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Updated: Aug 15, 2026

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

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Expression of LA45 reactive beta 2-microglobulin free HLA class I alpha-chains on activated T-cells is regulated by

W F Pickl1, W Holter, J Stöckl

  • 1Institute for Immunology, University of Vienna, Austria.

Tissue Antigens
|July 1, 1996
PubMed

HLA Class I molecules on activated T cells are expressed as mAb W6/32 reactive heterodimers associated with beta 2-microglobulin (beta 2-m) and also as mAb LA45 reactive beta 2-m free HLA Class I alpha-chains. However, the regulation of free alpha-chain expression remained enigmatic. Here we show, that the amount of cell surface expressed free heavy chains is influenced by two distinct mechanisms. Firstly, a proportion of expressed molecules are cleaved and give rise to a soluble pool of HLA Class I molecules. We provide evidence that, besides the previously described constitutive release of free alpha chains, a second phorbol ester inducible release mechanism involving activation of protein kinase C (PKC) does exist. We demonstrate that both the constitutive and the enhanced release of LA45 reactive HLA Class I alpha-chains are the consequence of a cell membrane bound proteolytic activity with the characteristics of a 1, 10 phenanthroline sensitive metalloprotease. Secondly, we report that a distinct fraction of mAb tagged free alpha-chains is internalized via an n-ethylmaleimide sensitive pathway. Together, this data suggests that the expression of free alpha-chains is regulated by pathways governing release and internalization.

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