Abstract
The CD3-T cell receptor (TcR) complex is central to the immune response. Upon binding by specific ligands, internalized CD3-TcR molecules increase, and either T cell response or unresponsiveness may ensue depending on the triggering conditions. Using semi-solid agar culture, we have shown previously that quiescent CD4 but not CD8 lymphocytes generate clonal colonies under phytohaemagglutinin stimulation. Here we have demonstrated that the agar induces selective CD3-TcR modulation in the CD8 and not in the CD4 subset. CD8 lymphocytes preactivated in liquid culture and recultured in agar with exogenous recombinant interleukin-2 generate colonies with a modulated CD3-TcR surface expression. The peptides composing the CD3-TcR complex are synthesized in CD8 colonies as well as in CD4; however, the CD3 gamma chain is phosphorylated at a higher level in CD8 colonies. A component of the agar polymer, absent in agarose, appears to be the ligand that induces differential CD3-TcR modulation in the CD8 subset. In contrast to agar culture, CD8 colonies can be derived from quiescent CD8 lymphocytes in agarose. These CD8 colonies express unmodulated CD-TcR. CD3-TcR modulation with anti-CD3 monoclonal antibody prior to culturing in agarose inhibits the colony formation. We conclude that given triggering conditions can result in both CD3-TcR modulation and inhibition of the proliferative response selectively in the CD8 lymphocyte subset and not in the CD4.
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- Alarcon B., Berkhout B., Breitmeyer J., Terhorst C. Assembly of the human T cell receptor-CD3 complex takes place in the endoplasmic reticulum and involves intermediary complexes between the CD3-gamma.delta.epsilon core and single T cell receptor alpha or beta chains. J Biol Chem. 1988 Feb 25;263(6):2953–2961. [PubMed] [Google Scholar]
- Alexander D. R., Cantrell D. A. Kinases and phosphatases in T-cell activation. Immunol Today. 1989 Jun;10(6):200–205. doi: 10.1016/0167-5699(89)90325-3. [DOI] [PubMed] [Google Scholar]
- Allison J. P., Lanier L. L. Structure, function, and serology of the T-cell antigen receptor complex. Annu Rev Immunol. 1987;5:503–540. doi: 10.1146/annurev.iy.05.040187.002443. [DOI] [PubMed] [Google Scholar]
- Bolen J. B., Veillette A., Schwartz A. M., Deseau V., Rosen N. Analysis of pp60c-src in human colon carcinoma and normal human colon mucosal cells. Oncogene Res. 1987 Jul;1(2):149–168. [PubMed] [Google Scholar]
- Borst J., Alexander S., Elder J., Terhorst C. The T3 complex on human T lymphocytes involves four structurally distinct glycoproteins. J Biol Chem. 1983 Apr 25;258(8):5135–5141. [PubMed] [Google Scholar]
- Borst J., Prendiville M. A., Terhorst C. The T3 complex on human thymus-derived lymphocytes contains two different subunits of 20 kDa. Eur J Immunol. 1983 Jul;13(7):576–580. doi: 10.1002/eji.1830130712. [DOI] [PubMed] [Google Scholar]
- Campana D., Thompson J. S., Amlot P., Brown S., Janossy G. The cytoplasmic expression of CD3 antigens in normal and malignant cells of the T lymphoid lineage. J Immunol. 1987 Jan 15;138(2):648–655. [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]
- Cantrell D., Davies A. A., Londei M., Feldman M., Crumpton M. J. Association of phosphorylation of the T3 antigen with immune activation of T lymphocytes. Nature. 1987 Feb 5;325(6104):540–542. doi: 10.1038/325540a0. [DOI] [PubMed] [Google Scholar]
- Chilson O. P., Kelly-Chilson A. E. Mitogenic lectins bind to the antigen receptor on human lymphocytes. Eur J Immunol. 1989 Feb;19(2):389–396. doi: 10.1002/eji.1830190225. [DOI] [PubMed] [Google Scholar]
- Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
- Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
- Davis L. S., Wacholtz M. C., Lipsky P. E. The induction of T cell unresponsiveness by rapidly modulating CD3. J Immunol. 1989 Feb 15;142(4):1084–1094. [PubMed] [Google Scholar]
- Farcet J. P., Gourdin M. F., Calvo C., Oudrhiri N., Divine M., Bouguet J., Fradelizzi D., Senik A., Reyes F. A subset of OKT4+ peripheral T cells can generate colonies containing mixed progeny with OKT4+ helper and OKT8+ suppressor cells. Eur J Immunol. 1985 Oct;15(10):1067–1073. doi: 10.1002/eji.1830151020. [DOI] [PubMed] [Google Scholar]
- Friedrich B., Gullberg M. The role of protein kinase C in early activation vs. growth of T lymphocytes. Eur J Immunol. 1988 Mar;18(3):489–492. doi: 10.1002/eji.1830180327. [DOI] [PubMed] [Google Scholar]
- Koning F., Lew A. M., Maloy W. L., Valas R., Coligan J. E. The biosynthesis and assembly of T cell receptor alpha- and beta-chains with the CD3 complex. J Immunol. 1988 May 1;140(9):3126–3134. [PubMed] [Google Scholar]
- Krangel M. S. Endocytosis and recycling of the T3-T cell receptor complex. The role of T3 phosphorylation. J Exp Med. 1987 Apr 1;165(4):1141–1159. doi: 10.1084/jem.165.4.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Minami Y., Samelson L. E., Klausner R. D. Internalization and cycling of the T cell antigen receptor. Role of protein kinase C. J Biol Chem. 1987 Sep 25;262(27):13342–13347. [PubMed] [Google Scholar]
- Ohashi P. S., Mak T. W., Van den Elsen P., Yanagi Y., Yoshikai Y., Calman A. F., Terhorst C., Stobo J. D., Weiss A. Reconstitution of an active surface T3/T-cell antigen receptor by DNA transfer. Nature. 1985 Aug 15;316(6029):606–609. doi: 10.1038/316606a0. [DOI] [PubMed] [Google Scholar]
- Oudrhiri N., Farcet J. P., Gourdin M. F., Divine M., Bouguet J., Fradelizi D., Reyes F. Mechanism of accessory cell requirement in inducing IL 2 responsiveness by human T4 lymphocytes that generate colonies under PHA stimulation. J Immunol. 1985 Sep;135(3):1813–1818. [PubMed] [Google Scholar]
- Pantaleo G., Olive D., Poggi A., Pozzan T., Moretta L., Moretta A. Antibody-induced modulation of the CD3/T cell receptor complex causes T cell refractoriness by inhibiting the early metabolic steps involved in T cell activation. J Exp Med. 1987 Aug 1;166(2):619–624. doi: 10.1084/jem.166.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pettey C. L., Alarcon B., Malin R., Weinberg K., Terhorst C. T3-p28 is a protein associated with the delta and epsilon chains of the T cell receptor-T3 antigen complex during biosynthesis. J Biol Chem. 1987 Apr 5;262(10):4854–4859. [PubMed] [Google Scholar]
- Rivas A., Takada S., Koide J., Sonderstrup-McDevitt G., Engleman E. G. CD4 molecules are associated with the antigen receptor complex on activated but not resting T cells. J Immunol. 1988 May 1;140(9):2912–2918. [PubMed] [Google Scholar]
- Sussman J. J., Bonifacino J. S., Lippincott-Schwartz J., Weissman A. M., Saito T., Klausner R. D., Ashwell J. D. Failure to synthesize the T cell CD3-zeta chain: structure and function of a partial T cell receptor complex. Cell. 1988 Jan 15;52(1):85–95. doi: 10.1016/0092-8674(88)90533-8. [DOI] [PubMed] [Google Scholar]
- Thomas M. L., Lefrançois L. Differential expression of the leucocyte-common antigen family. Immunol Today. 1988 Oct;9(10):320–326. doi: 10.1016/0167-5699(88)91326-6. [DOI] [PubMed] [Google Scholar]
- Van Wauwe J. P., Goossens J., Van Nyen G. Inhibition of lymphocyte proliferation by monoclonal antibody directed against the T3 antigen on human T cells. Cell Immunol. 1984 Jul;86(2):525–534. doi: 10.1016/0008-8749(84)90408-8. [DOI] [PubMed] [Google Scholar]
- Weiss A., Stobo J. D. Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line. J Exp Med. 1984 Nov 1;160(5):1284–1299. doi: 10.1084/jem.160.5.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weissman A. M., Samelson L. E., Klausner R. D. A new subunit of the human T-cell antigen receptor complex. Nature. 1986 Dec 4;324(6096):480–482. doi: 10.1038/324480a0. [DOI] [PubMed] [Google Scholar]
- Wood P. J., Socarras S., Streilein J. W. Modification of the cytotoxic T cell repertoire in neonatal tolerance. Evidence for preferential survival of cells with low avidity for tolerogen. J Immunol. 1987 Nov 15;139(10):3236–3244. [PubMed] [Google Scholar]



