Immunoglobulins derived from sera containing anti- antiidiotypic antibodies (Ab2) generated in renal transplant recipients after OKT3 monoclonal antibody therapy, as reported in our previous study (1), have now been proved to bind to several bands of T cell membrane lysates (TCML) in immunoblotting analyses ranging in molecular weight from 40 to 55 KD. These sera also blocked the expression of the ligand binding to WT31 in flow cytometry. WT31 is a MAb that recognizes a common determinant on the T cell receptor (TCR). Immunoglobulins from these sera suppressed the activation of normal peripheral blood T lymphocytes (PBT) induced by OKT3. All patients (7/32) who developed this Ab2 had distinct culture-proved cytomegaloviral infections. In further immunoblotting studies, αFl, another MAb recognizing the framework of the TCR α chain, more deeply inserted in the T cell membrane, also showed binding to protein bands of cytomegalovirus pellet lysates derived from virus-infected embryonic fibroblasts. In addition, αFl showed positive binding to several ligands in the membrane lysate of CMV-infected, but not noninfected MRC-5 cells. An anti-CMV MAb recognizing late nuclear antigen (LAb), also strongly bound to a ∼50 KD band of TCML and several bands (∼34, ∼40, and ∼50 KD) of H33HJAJ1 (human T leukemia) cell lysate. Furthermore, αFl immunoprecipitated a -96 KD ligand of CMV-infected MRC5 lysate that had the same electrophoretic mobility as one of the proteins precipi- table with LAb. Both LAb and aFl also showed positive binding to paraformaldehyde-fixed and Triton X-100- permeabilized PBT in flow cytometry. Sera containing Ab2 blocked αFl binding to acetone-fixed cytofuged PBT preparations on slides. Moreover, both αFl and LAb inhibited mitogen-stimulated lymphocyte activation in vitro. These data support the notion that T cell functional abnormalities associated with CMV infection observed after treatment of transplant recipients with anti-T cell monoclonals might be caused by binding to T cell ligands by a variety of crossreacting human Igs operative in a regulatory network. Confirmatory evidence is the effect of MAbs generated against CMV virion epitopes crossreacting with T cell ligands, and vice versa.
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