A 44 kilodalton cell surface homodimer regulates interleukin 2 production by activated human T lymphocytes.
We previously described a cell surface antigen, termed Tp44, detected by monoclonal antibody 9.3 on approximately 80% of mature human T lymphocytes. Analysis by SDS-polyacrylamide gel electrophoresis and isoelectric focusing demonstrated that this antigen consists of two identical 44 kilodalton glycopeptides that form a disulfide-linked homodimer. Competitive binding experiments showed that antibody 9.3 and an anti-CD3 antibody (64.1) recognize distinct antigenic determinants; furthermore, the binding of antibody 9.3 was unaffected by prior modulation of CD3. Thus, Tp44 has no detectable cell surface association with CD3. By itself, antibody 9.3 had no detectable effect on either IL 2 receptor expression or IL 2 release, and did not cause T cell proliferation even when monocytes were present and exogenous IL 2 was provided, indicating that binding of antibody 9.3 does not provide a primary signal for T cell activation. However, the proliferative responses of T lymphocytes activated by phytohemagglutinin, concanavalin A, or an anti-CD3 monoclonal antibody were strikingly enhanced in the presence of antibody 9.3, an effect associated with increased IL 2 receptor expression and increased IL 2 secretion. Antibody 9.3 enabled anti-CD3-Sepharose-activated T cells and anti-CD3 antibody-activated Jurkat cells to release IL 2 in the absence of monocytes. Fab fragments of antibody 9.3 had no effect on anti-CD3-induced IL 2 release by Jurkat cells, whereas F(ab')2 fragments had activity comparable to that of unmodified antibody, indicating that bivalent binding of Tp44 molecules is required for IL 2 secretion. Together, these results suggest that TP44 may function as a receptor for accessory signals in the activation of T cells.
Martin
P J
PJ
Ledbetter
J A
JA
Morishita
Y
Y
June
C H
CH
Beatty
P G
PG
Hansen
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008970:Molecular Weight; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000378:metabolism; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2