Journal article
Correlation of CD2 binding and functional properties of multimeric and monomeric lymphocyte function-associated antigen 3.
- Abstract:
- LFA-3 was purified with an intact (mLFA-3) or an enzymatically removed membrane-anchoring domain (sLFA-3). Gel filtration and sucrose gradient sedimentation showed sLFA-3 to be a single highly glycosylated polypeptide chain in solution, while mLFA-3 formed micelles of 8 LFA-3 monomers. 125I-mLFA-3 bound to Jurkat T leukemic cell surface CD2 with much higher avidity than sLFA-3. mLFA-3 binding had characteristics of a multivalent interaction with cell surface CD2 and had an avidity of 1.5 nM for Jurkat cells and 12 nM for resting T cells. Two CD2 mAbs tested did not block mLFA-3 binding: 9-1 and CD2.1. These mAbs were tested in combination with LFA-3 for their ability to activate T cells. The combination of mLFA-3 and CD2.1 mAbs induced a rapid increase in cytosolic free Ca2+ in Jurkat cells which was proportional to mLFA-3 occupation of CD2 sites. sLFA-3 showed no activity in the Ca2+ flux assay. The combination of mLFA-3 and the CD2.1 mAbs significantly stimulated proliferation of PBMC. The combination of mLFA-3 and 9-1 mAbs was weakly or not mitogenic for the same cells. The combination of CD2.1 and sLFA-3 at concentrations up to 480 nM was not consistently mitogenic. Therefore, monomeric LFA-3/CD2 interaction appears to have a relatively low affinity, while multimeric LFA-3 binds with high avidity. T cell activation by binding of LFA-3 to CD2 appears to require occupation of 10(4) to 10(5) CD2 sites, which is likely to occur during adhesion, but is rare in receptor systems with soluble ligands.
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- Journal:
- Journal of experimental medicine More from this journal
- Volume:
- 169
- Issue:
- 2
- Pages:
- 503-517
- Publication date:
- 1989-02-01
- DOI:
- EISSN:
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1540-9538
- ISSN:
-
0022-1007
- Language:
-
English
- Keywords:
-
- Pubs id:
-
pubs:482708
- UUID:
-
uuid:a6016d05-6553-4b74-9aef-155bb01f092f
- Local pid:
-
pubs:482708
- Source identifiers:
-
482708
- Deposit date:
-
2014-09-14
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- Copyright date:
- 1989
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