Abstract
In this report, we describe a novel activation antigen that appears very early after T cell activation and is absent in resting lymphocytes, through which agonistic proliferative signals can be triggered by mAb binding. It has been designated as activation inducer molecule (AIM) and is a disulphide-linked heterodimeric structure containing two polypeptide chains of Mr 33,000 and 27,000. The expression of AIM can be induced by different activation stimuli such as PMA, PHA, or anti-CD3 mAb, but not by the Ca2+ ionophore A23187, and it precedes the expression of other activation molecules such as 4F2 or the IL-2-R. Once AIM antigens are expressed on lymphocytes after stimulation with submitogenic doses of PMA, the binding of anti-AIM mAbs triggers a strong proliferative response. Furthermore, a comitogenic effect of the anti-AIM mAbs is exerted in the presence of either PHA or anti-CD3 mAb. The activation of lymphocytes through AIM antigens induces both IL-2 and IL-2-R receptor synthesis and is inhibited by anti-IL-2-R mAbs.
Full Text
The Full Text of this article is available as a PDF (1.2 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Burns G. F., Boyd A. W., Beverley P. C. Two monoclonal anti-human T lymphocyte antibodies have similar biologic effects and recognize the same cell surface antigen. J Immunol. 1982 Oct;129(4):1451–1457. [PubMed] [Google Scholar]
- Burns G. F., Triglia T., Werkmeister J. A., Begley C. G., Boyd A. W. TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors. J Exp Med. 1985 May 1;161(5):1063–1078. doi: 10.1084/jem.161.5.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantrell D. A., Davies A. A., Crumpton M. J. Activators of protein kinase C down-regulate and phosphorylate the T3/T-cell antigen receptor complex of human T lymphocytes. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8158–8162. doi: 10.1073/pnas.82.23.8158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carrel S., Isler P., Salvi S., Giuffrè L., Pantaleo G., Mach J. P., Cerottini J. C. Identification of a novel 45-kDa cell surface molecule involved in activation of the human Jurkat T cell line. Eur J Immunol. 1987 Oct;17(10):1395–1402. doi: 10.1002/eji.1830171002. [DOI] [PubMed] [Google Scholar]
- Carrel S., Salvi S., Giuffrè L., Isler P., Cerottini J. C. A novel 90-kDa polypeptide (Tp90) possibly involved in an antigen-independent pathway of T cell activation. Eur J Immunol. 1987 Jun;17(6):835–841. doi: 10.1002/eji.1830170616. [DOI] [PubMed] [Google Scholar]
- Carrera A. C., Sanchez-Madrid F., Lopez-Botet M., Bernabeu C., De Landazuri M. O. Involvement of the CD4 molecule in a post-activation event on T cell proliferation. Eur J Immunol. 1987 Feb;17(2):179–186. doi: 10.1002/eji.1830170205. [DOI] [PubMed] [Google Scholar]
- Cosulich M. E., Rubartelli A., Risso A., Cozzolino F., Bargellesi A. Functional characterization of an antigen involved in an early step of T-cell activation. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4205–4209. doi: 10.1073/pnas.84.12.4205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cotner T., Williams J. M., Christenson L., Shapiro H. M., Strom T. B., Strominger J. Simultaneous flow cytometric analysis of human T cell activation antigen expression and DNA content. J Exp Med. 1983 Feb 1;157(2):461–472. doi: 10.1084/jem.157.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dancey G. F., Yasuda T., Kinsky S. C. Effect of liposomal model membrane composition on immunogenicity. J Immunol. 1978 Apr;120(4):1109–1113. [PubMed] [Google Scholar]
- Fleischer B. A novel pathway of human T cell activation via a 103 kD T cell activation antigen. J Immunol. 1987 Mar 1;138(5):1346–1350. [PubMed] [Google Scholar]
- Fleischer B., Schendel D. J., Von Steldern D. Triggering of the lethal hit in human cytotoxic T lymphocytes: a functional role for a 103-kDa T cell-specific activation antigen. Eur J Immunol. 1986 Jul;16(7):741–746. doi: 10.1002/eji.1830160705. [DOI] [PubMed] [Google Scholar]
- Fox D. A., Hussey R. E., Fitzgerald K. A., Acuto O., Poole C., Palley L., Daley J. F., Schlossman S. F., Reinherz E. L. Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody. J Immunol. 1984 Sep;133(3):1250–1256. [PubMed] [Google Scholar]
- Fox R. I., Hueniken M., Fong S., Behar S., Royston I., Singhal S. K., Thompson L. A novel cell surface antigen (T305) found in increased frequency on acute leukemia cells and in autoimmune disease states. J Immunol. 1983 Aug;131(2):762–767. [PubMed] [Google Scholar]
- Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
- Galfrè G., Milstein C. Preparation of monoclonal antibodies: strategies and procedures. Methods Enzymol. 1981;73(Pt B):3–46. doi: 10.1016/0076-6879(81)73054-4. [DOI] [PubMed] [Google Scholar]
- Gordon J., Rowe M., Walker L., Guy G. Ligation of the CD23,p45 (BLAST-2,EBVCS) antigen triggers the cell-cycle progression of activated B lymphocytes. Eur J Immunol. 1986 Sep;16(9):1075–1080. doi: 10.1002/eji.1830160908. [DOI] [PubMed] [Google Scholar]
- Hara T., Fu S. M., Hansen J. A. Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen). J Exp Med. 1985 Jun 1;161(6):1513–1524. doi: 10.1084/jem.161.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hara T., Fu S. M. Human T cell activation. I. Monocyte-independent activation and proliferation induced by anti-T3 monoclonal antibodies in the presence of tumor promoter 12-o-tetradecanoyl phorbol-13 acetate. J Exp Med. 1985 Apr 1;161(4):641–656. doi: 10.1084/jem.161.4.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hara T., Jung L. K., Bjorndahl J. M., Fu S. M. Human T cell activation. III. Rapid induction of a phosphorylated 28 kD/32 kD disulfide-linked early activation antigen (EA 1) by 12-o-tetradecanoyl phorbol-13-acetate, mitogens, and antigens. J Exp Med. 1986 Dec 1;164(6):1988–2005. doi: 10.1084/jem.164.6.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haynes B. F., Hemler M. E., Mann D. L., Eisenbarth G. S., Shelhamer J., Mostowski H. S., Thomas C. A., Strominger J. L., Fauci A. S. Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes. J Immunol. 1981 Apr;126(4):1409–1414. [PubMed] [Google Scholar]
- Hemler M. E., Jacobson J. G., Brenner M. B., Mann D., Strominger J. L. VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation. Eur J Immunol. 1985 May;15(5):502–508. doi: 10.1002/eji.1830150515. [DOI] [PubMed] [Google Scholar]
- Hemler M. E., Sanchez-Madrid F., Flotte T. J., Krensky A. M., Burakoff S. J., Bhan A. K., Springer T. A., Strominger J. L. Glycoproteins of 210,000 and 130,000 m.w. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines. J Immunol. 1984 Jun;132(6):3011–3018. [PubMed] [Google Scholar]
- Hercend T., Ritz J., Schlossman S. F., Reinherz E. L. Comparative expression of T9, T10, and Ia antigens on activated human T cell subsets. Hum Immunol. 1981 Nov;3(3):247–259. doi: 10.1016/0198-8859(81)90021-5. [DOI] [PubMed] [Google Scholar]
- Holter W., Fischer G. F., Majdic O., Stockinger H., Knapp W. T cell stimulation via the erythrocyte receptor. Synergism between monoclonal antibodies and phorbol myristate acetate without changes of free cytoplasmic Ca++ levels. J Exp Med. 1986 Mar 1;163(3):654–664. doi: 10.1084/jem.163.3.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holter W., Majdic O., Stockinger H., Knapp W. Analysis of T cell activation with a non-mitogenic anti CD3 antibody and the phorbol ester TPA. Clin Exp Immunol. 1985 Dec;62(3):600–606. [PMC free article] [PubMed] [Google Scholar]
- Ko H. S., Fu S. M., Winchester R. J., Yu D. T., Kunkel H. G. Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med. 1979 Aug 1;150(2):246–255. doi: 10.1084/jem.150.2.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lazarovits A. I., Moscicki R. A., Kurnick J. T., Camerini D., Bhan A. K., Baird L. G., Erikson M., Colvin R. B. Lymphocyte activation antigens. I. A monoclonal antibody, anti-Act I, defines a new late lymphocyte activation antigen. J Immunol. 1984 Oct;133(4):1857–1862. [PubMed] [Google Scholar]
- Lefrançois L., Bevan M. J. Functional modifications of cytotoxic T-lymphocyte T200 glycoprotein recognized by monoclonal antibodies. Nature. 1985 Apr 4;314(6010):449–452. doi: 10.1038/314449a0. [DOI] [PubMed] [Google Scholar]
- Leonard W. J., Depper J. M., Uchiyama T., Smith K. A., Waldmann T. A., Greene W. C. A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor. Nature. 1982 Nov 18;300(5889):267–269. doi: 10.1038/300267a0. [DOI] [PubMed] [Google Scholar]
- Malissen B., Rebai N., Liabeuf A., Mawas C. Human cytotoxic T cell structures associated with expression of cytolysis. I. Analysis at the clonal cell level of the cytolysis-inhibiting effect of 7 monoclonal antibodies. Eur J Immunol. 1982 Sep;12(9):739–747. doi: 10.1002/eji.1830120908. [DOI] [PubMed] [Google Scholar]
- Mastro A. M., Mueller G. C. Synergistic action of phorbol esters in mitogen-activated bovine lymphocytes. Exp Cell Res. 1974 Sep;88(1):40–46. doi: 10.1016/0014-4827(74)90615-6. [DOI] [PubMed] [Google Scholar]
- Mendelsohn J., Trowbridge I., Castagnola J. Inhibition of human lymphocyte proliferation by monoclonal antibody to transferrin receptor. Blood. 1983 Oct;62(4):821–826. [PubMed] [Google Scholar]
- Meuer S. C., Hodgdon J. C., Hussey R. E., Protentis J. P., Schlossman S. F., Reinherz E. L. Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones. J Exp Med. 1983 Sep 1;158(3):988–993. doi: 10.1084/jem.158.3.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meuer S. C., Hussey R. E., Fabbi M., Fox D., Acuto O., Fitzgerald K. A., Hodgdon J. C., Protentis J. P., Schlossman S. F., Reinherz E. L. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984 Apr;36(4):897–906. doi: 10.1016/0092-8674(84)90039-4. [DOI] [PubMed] [Google Scholar]
- Michalak M., Quackenbush E. J., Letarte M. Inhibition of Na+/Ca2+ exchanger activity in cardiac and skeletal muscle sarcolemmal vesicles by monoclonal antibody 44D7. J Biol Chem. 1986 Jan 5;261(1):92–95. [PubMed] [Google Scholar]
- Miyawaki T., Yachie A., Uwadana N., Ohzeki S., Nagaoki T., Taniguchi N. Functional significance of Tac antigen expressed on activated human T lymphocytes: Tac antigen interacts with T cell growth factor in cellular proliferation. J Immunol. 1982 Dec;129(6):2474–2478. [PubMed] [Google Scholar]
- Moretta A., Pantaleo G., Lopez-Botet M., Moretta L. Involvement of T44 molecules in an antigen-independent pathway of T cell activation. Analysis of the correlations to the T cell antigen-receptor complex. J Exp Med. 1985 Sep 1;162(3):823–838. doi: 10.1084/jem.162.3.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pulido R., Cebrián M., Acevedo A., de Landázuri M. O., Sánchez-Madrid F. Comparative biochemical and tissue distribution study of four distinct CD45 antigen specificities. J Immunol. 1988 Jun 1;140(11):3851–3857. [PubMed] [Google Scholar]
- Reinherz E. L., Meuer S., Fitzgerald K. A., Hussey R. E., Levine H., Schlossman S. F. Antigen recognition by human T lymphocytes is linked to surface expression of the T3 molecular complex. Cell. 1982 Oct;30(3):735–743. doi: 10.1016/0092-8674(82)90278-1. [DOI] [PubMed] [Google Scholar]
- Rozengurt E., Rodriguez-Pena A., Coombs M., Sinnett-Smith J. Diacylglycerol stimulates DNA synthesis and cell division in mouse 3T3 cells: role of Ca2+-sensitive phospholipid-dependent protein kinase. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5748–5752. doi: 10.1073/pnas.81.18.5748. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanchez-Madrid F., Davignon D., Martz E., Springer T. A. Antigens involved in mouse cytolytic T-lymphocyte (CTL)-mediated killing: functional screening and topographic relationship. Cell Immunol. 1982 Oct;73(1):1–11. doi: 10.1016/0008-8749(82)90431-2. [DOI] [PubMed] [Google Scholar]
- Sanchez-Madrid F., Krensky A. M., Ware C. F., Robbins E., Strominger J. L., Burakoff S. J., Springer T. A. Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7489–7493. doi: 10.1073/pnas.79.23.7489. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanchez-Madrid F., Szklut P., Springer T. A. Stable hamster-mouse hybridomas producing IgG and IgM hamster monoclonal antibodies of defined specificity. J Immunol. 1983 Jan;130(1):309–312. [PubMed] [Google Scholar]
- Sanchez-Madrid F., Toribio M. L., Gambón F., de Landazuri M. O. Cell surface molecular changes on the activation of human thymocytes. J Immunol. 1985 Dec;135(6):3938–3943. [PubMed] [Google Scholar]
- Schreiber A. B., Lax I., Yarden Y., Eshhar Z., Schlessinger J. Monoclonal antibodies against receptor for epidermal growth factor induce early and delayed effects of epidermal growth factor. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7535–7539. doi: 10.1073/pnas.78.12.7535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suciu-Foca N., Reed E., Rubinstein P., MacKenzie W., Ng A. K., King D. W. A late-differentiation antigen associated with the helper inducer function of human T cells. Nature. 1985 Dec 5;318(6045):465–467. doi: 10.1038/318465a0. [DOI] [PubMed] [Google Scholar]
- Sánchez-Madrid F., De Landázuri M. O., Morago G., Cebrián M., Acevedo A., Bernabeu C. VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization. Eur J Immunol. 1986 Nov;16(11):1343–1349. doi: 10.1002/eji.1830161106. [DOI] [PubMed] [Google Scholar]
- Trowbridge I. S., Lopez F. Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1175–1179. doi: 10.1073/pnas.79.4.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trowbridge I. S., Omary M. B. Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin. Proc Natl Acad Sci U S A. 1981 May;78(5):3039–3043. doi: 10.1073/pnas.78.5.3039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Truneh A., Albert F., Golstein P., Schmitt-Verhulst A. M. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester. Nature. 1985 Jan 24;313(6000):318–320. doi: 10.1038/313318a0. [DOI] [PubMed] [Google Scholar]
- Van Wauwe J. P., De Mey J. R., Goossens J. G. OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties. J Immunol. 1980 Jun;124(6):2708–2713. [PubMed] [Google Scholar]