|
|
||||||||
The Journal of Immunology, Vol 148, Issue 3 695-701, Copyright © 1992 by American Association of Immunologists
ARTICLES |
PW Parren, PA Warmerdam, LC Boeije, PJ Capel, JG van de Winkel and LA Aarden
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
T cell activation induced by mouse anti-CD3 mAb has shown to be dependent on the Ig isotype of these antibodies. A study of isotype dependency of human antibodies, however, seems more relevant to human effector systems, especially in view of the availability of humanized antibodies for clinical applications. We constructed a panel of mouse and mouse/human chimeric anti-CD3 mAb, which differ only in their CH region and hence have identical binding sites and affinity. By using these antibodies, we now studied their ability to induce T cell proliferation in human PBMC and analyzed the classes of IgG FcR involved in these responses. The human (h)IgG1, hIgG3, and hIgG4, as well as mouse (m)IgG2a and mIgG3 anti-CD3 mAb induced an Fc gamma RI (CD64)-dependent T cell proliferation in all donors. Activation with hIgG2 and mIgG1 anti-CD3 mAb was observed to be mediated via the low affinity Fc gamma RII (CD32). It was found that leukocytes in a normal donor population display a functional polymorphism with respect to hIgG2 anti-CD3 responsiveness. This polymorphism was found to be inversely related to the previously defined Fc gamma RII-polymorphism to mIgG1 anti-CD3 mAb. Monocytes expressing the Fc gamma RII mIgG1 low responder (LR) allele support hIgG2 anti-CD3 induced T cell proliferation efficiently, whereas cells homozygous for the Fc gamma RII mIgG1 high responder (HR) allele do not. This observation could be confirmed in T cell activation studies using hFc gamma RIIa-transfected mouse fibroblasts, expressing either the mIgG1 anti-CD3 HR or LR Fc gamma RII-encoding cDNA.
This article has been cited by other articles:
![]() |
T. Lehrnbecher, C. B. Foster, S. Zhu, S. F. Leitman, L. R. Goldin, K. Huppi, and S. J. Chanock Variant Genotypes of the Low-Affinity Fcgamma Receptors in Two Control Populations and a Review of Low-Affinity Fcgamma Receptor Polymorphisms in Control and Disease Populations Blood, December 15, 1999; 94(12): 4220 - 4232. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. F. Norris, L. Pricop, S. S. Millard, S. M. Taylor, S. Surrey, E. Schwartz, J. E. Salmon, and S. E. McKenzie A Naturally Occurring Mutation in FCgamma RIIA: A Q to K127 Change Confers Unique IgG Binding Properties to the R131 Allelic Form of the Receptor Blood, January 15, 1998; 91(2): 656 - 662. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |