Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors.

JL Browning, I Dougas, A Ngam-ek… - … (Baltimore, Md.: 1950 …, 1995 - journals.aai.org
JL Browning, I Dougas, A Ngam-ek, PR Bourdon, BN Ehrenfels, K Miatkowski, M Zafari…
Journal of immunology (Baltimore, Md.: 1950), 1995journals.aai.org
Lymphotoxin (LT) is a cytokine related to TNF, found in human systems in both secreted and
membrane bound forms. The well characterized secreted form is a trimer of a single protein,
LT-alpha, whereas the surface form is composed of a complex between two related
molecules, LT-alpha and LT-beta. Because there is a distinct receptor for the complex, the
membrane form is believed to signal via events different from those elicited by TNF and
secreted LT-alpha. By using a battery of anti-LT-alpha and LT-beta mAbs, it is clear that two …
Abstract
Lymphotoxin (LT) is a cytokine related to TNF, found in human systems in both secreted and membrane bound forms. The well characterized secreted form is a trimer of a single protein, LT-alpha, whereas the surface form is composed of a complex between two related molecules, LT-alpha and LT-beta. Because there is a distinct receptor for the complex, the membrane form is believed to signal via events different from those elicited by TNF and secreted LT-alpha. By using a battery of anti-LT-alpha and LT-beta mAbs, it is clear that two LT surface forms exist on the surface of PMA-activated II-23 cells, a human T cell hybridoma. Assuming that these surface forms are trimers, a minor form appears early after induction having an apparent stoichiometry of LT-alpha 2/beta 1 and is recognized by one group of anti-LT-alpha mAbs and the p55-TNF receptor. The second and predominant form has an apparent LT-alpha 1/beta 2 composition and is recognized by a second group of pantrophic anti-LT-alpha mAbs and the LT-beta receptor. Neither of the heteromeric forms nor a putative LT-beta homotrimeric form were found to be secreted. The properties of surface LT on the II-23 cell system were similar to those of the surface LT forms on Chinese hamster ovary cells transfected with both LT-alpha and LT-beta genes and a number of lymphoid tumor lines. These experiments point toward the LT-alpha 1/beta 2 complex as the predominant membrane form of LT on the lymphocyte surface, and this complex is the primary ligand for the LT-beta receptor.
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