A 19-kDa human erythrocyte molecule H19 is involved in rosettes, present on nucleated cells, and required for T cell activation. Comparison of the roles of H19 and LFA-3 molecules in T cell activation.
We have previously described a molecule on the SRBC surface which, in addition to the sheep equivalent of LFA-3, is involved in the process of rosette formation. It is made of a single, 14- to 19-kDa, polypeptide chain, and we termed this molecule S14. We have now identified, on the human E a molecule with a similar Mr albeit somewhat higher (19 kDa). The mAb against H19 efficiently block autologous or homologous rosettes by binding to human E. In addition, purified H19 molecules block rosettes made with human E and SRBC in a dose-dependent manner. The H19 molecule, like LFA-3, is not limited to the E surface, but is also present on many nucleated cells, including T cells and monocytes. Moreover H19, like LFA-3, is required for T cell activation: when we stimulated whole PBMC anti-H19 blocked [H3]TdR incorporation triggered via CD3, but not via CD2, in contrast to anti-LFA-3 that inhibited activation via both pathways. When a mixture of highly purified T-PBL and autologous paraformaldehyde fixed accessory cells (AC) was cultivated, anti-H19 or anti-LFA-3 mAb bound to AC blocked T cell proliferation. When high amounts of rIL-1 (100 U/ml) were added to purified T-PBL, no AC were required to sustain their proliferation upon stimulation via CD2, contrary to stimulation via CD3. When lower amounts of rIL-1 (10 U/ml) were used, fixed AC were still necessary to sustain proliferation via CD2. In this latter situation, anti-H19 mAb bound to AC could no longer inhibit T cell proliferation, whereas the anti-LFA-3 mAb was still inhibitory. When T-PBL were stimulated via CD2 in the presence of 100 U/ml of rIL-1, anti-LFA-3 did not induce any inhibition. Thus the inhibitory effect of anti-H19 and anti-LFA-3 mAb can both be accounted for by an effect on the AC molecules only, and not on the T cell molecules. F(ab')2 fragments of anti-H19 mAb produced the same pattern of inhibition as the whole Ig molecule, excluding an effect via the FcR. Moreover, purified preparations of the H19 molecules also produced inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
Groux
H
H
Laboratoire d'Immunologie des Tumeurs de l'Enfant, Institut Gustave-Roussy, Villejuif, France.
Huet
S
S
Aubrit
F
F
Tran
H C
HC
Boumsell
L
L
Bernard
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D001667:Binding, Competitive; D018968:CD58 Antigens; D004910:Erythrocyte Membrane / Q000032:analysis* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000032:analysis*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D008970:Molecular Weight; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000032:analysis / Q000276:immunology*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018968:CD58 Antigens; D008562:Membrane Glycoproteins