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Modulation of antigen-induced T cell proliferation by alpha 2M-trypsin complexes.

J W Mannhalter, W Borth and M M Eibl
J Immunol April 15, 1986, 136 (8) 2792-2799;
J W Mannhalter
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W Borth
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M M Eibl
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Abstract

Proteinase-complexed alpha 2-macroglobulin (alpha 2M) could be shown to interfere with T cell proliferation in response to antigen presented by autologous antigen-pulsed monocytes (M phi) (antigen-induced M phi-T cell interaction, MTI). Addition of alpha 2M-trypsin (alpha 2M X T) complexes to cultures of T cells and antigen-pulsed M phi led to a dose-dependent decrease of T cell proliferation (up to 91% inhibition of the T cell response), whereas the same concentrations of free (native) alpha 2M had no effect on antigen-induced MTI. The observed interference with MTI could be attributed to residual enzymic activity of the alpha 2M X T complex. Addition of aprotinin, a low Mr protein proteinase inhibitor able to penetrate to the enzyme entrapped within the alpha 2M molecule and thus bind to and inactivate the enzyme's active site, resulted in a reversal of the alpha 2M X T-induced biological effect. Inactivation of the enzyme's active site within alpha 2M X T was monitored by a decrease in the hydrolytic activity of the complex. Kinetic studies (addition of alpha 2M X T 24 to 48 hr after culture onset was shown to be still inhibitory) indicated an effect at the level of the T cell or its mediators, but an overnight incubation of T cells with alpha 2M X T did not alter these cells' capacity to proliferate in response to an antigenic stimulus. An additional effect of alpha 2M X T on the antigen-presenting cell cannot be ruled out at present. However, alpha 2M X T did not alter the percentage of monocytes expressing HLA-DR, -DP, and -DQ or interfere with interleukin 1 release if added to M phi at concentrations that significantly inhibited MTI. Furthermore, incubation of M phi with alpha 2M X T for 1 hr before antigen pulsing had no effect on the M phi antigen presenting capacity.

  • Copyright © 1986 by American Association of Immunologists

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The Journal of Immunology
Vol. 136, Issue 8
15 Apr 1986
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Modulation of antigen-induced T cell proliferation by alpha 2M-trypsin complexes.
J W Mannhalter, W Borth, M M Eibl
The Journal of Immunology April 15, 1986, 136 (8) 2792-2799;

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Modulation of antigen-induced T cell proliferation by alpha 2M-trypsin complexes.
J W Mannhalter, W Borth, M M Eibl
The Journal of Immunology April 15, 1986, 136 (8) 2792-2799;
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Print ISSN 0022-1767        Online ISSN 1550-6606