The Costimulatory Activity of the CD26 Antigen Requires Dipeptidyl Peptidase IV Enzymatic Activity

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1993 May 15

PMID 7685106

Citations 46

Authors

T Tanaka

J Kameoka

A YARON

S F Schlossman

C Morimoto

Affiliations

Soon will be listed here.

Abstract

T cells have been shown to express CD26, a known ectoenzyme with dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) activity in its extracellular domain. CD26 can also deliver a second costimulatory signal and contribute to T-cell activation. In an earlier study, we established CD26-transfected Jurkat T-cell lines and demonstrated that monoclonal antibody-mediated crosslinking of CD26 and CD3 induced interleukin 2 (IL-2) production. To determine the contribution of DPPIV enzymatic activity to the costimulatory activity of CD26, human CD26 cDNA was mutated so that active-site serine was replaced by alanine. The mutant CD26 antigen lacked DPPIV enzyme activity but still retained reactivity with three anti-CD26 monoclonal antibodies directed against distinct epitopes of CD26. After stimulation with a combination of anti-CD26 and anti-CD3 antibodies, wild-type CD26 (DPPIV+)-transfected Jurkat cells produced substantially more IL-2 than did mutant CD26 (DPPIV-) or CD26- control transfectants. Nevertheless, the mutant CD26-transfected cells still produced significantly more IL-2 than did CD26- control transfectants. These results suggest that DPPIV activity plays an important but not absolute role in the co-stimulatory activity of CD26 in this system. We also found that wild-type CD26 (DPPIV+) transfectants produced more IL-2 than mutant CD26 (DPPIV-)-transfected cells or CD26- control transfectants when triggered by stimuli not involving CD26, such as anti-CD3 and phorbol ester. These results suggest that the DPPIV activity of CD26 functions to augment the cellular responses of CD26-transfected Jurkat cells to external stimuli mediated by CD26 and/or the CD3/T-cell receptor complex, thus enhancing IL-2 production.

Citing Articles

Implicit Flow Cytometric Diagnosis of Classic Hodgkin Lymphoma Using CD3CD4CD26 T-Cells.

Gravenmier C, Song J, Shao H J Clin Lab Anal. 2024; 38(17-18):e25096.

PMID: 39235202 PMC: 11484709. DOI: 10.1002/jcla.25096.

The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications.

Li D, Yuan S, Deng Y, Wang X, Wu S, Chen X Front Immunol. 2023; 14:1282890.

PMID: 38053999 PMC: 10694226. DOI: 10.3389/fimmu.2023.1282890.

Emerging Role of Dipeptidyl Peptidase-4 in Autoimmune Disease.

Huang J, Liu X, Wei Y, Li X, Gao S, Dong L Front Immunol. 2022; 13:830863.

PMID: 35309368 PMC: 8931313. DOI: 10.3389/fimmu.2022.830863.

Structure-based study of immune receptors as eligible binding targets of coronavirus SARS-CoV-2 spike protein.

Mobini S, Chizari M, Mafakher L, Rismani E, Rismani E J Mol Graph Model. 2021; 108:107997.

PMID: 34343818 PMC: 8317541. DOI: 10.1016/j.jmgm.2021.107997.

DPP4 inhibition mitigates ANG II-mediated kidney immune activation and injury in male mice.

Nistala R, Meuth A, Smith C, An J, Habibi J, Hayden M Am J Physiol Renal Physiol. 2021; 320(3):F505-F517.

PMID: 33522410 PMC: 7988815. DOI: 10.1152/ajprenal.00565.2020.

References

Nagatsu T, Hino M, Fuyamada H, Hayakawa T, Sakakibara S . New chromogenic substrates for X-prolyl dipeptidyl-aminopeptidase. Anal Biochem. 1976; 74(2):466-76. DOI: 10.1016/0003-2697(76)90227-x. View

De Meester I, Vanhoof G, Hendriks D, Demuth H, YARON A, Scharpe S . Characterization of dipeptidyl peptidase IV (CD26) from human lymphocytes. Clin Chim Acta. 1992; 210(1-2):23-34. DOI: 10.1016/0009-8981(92)90042-o. View

Fox D, Hussey R, Fitzgerald K, Acuto O, Poole C, Palley L . Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody. J Immunol. 1984; 133(3):1250-6. View

Kunkel T . Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985; 82(2):488-92. PMC: 397064. DOI: 10.1073/pnas.82.2.488. View

Fleischer B . A novel pathway of human T cell activation via a 103 kD T cell activation antigen. J Immunol. 1987; 138(5):1346-50. View

Streuli M, HALL L, Saga Y, Schlossman S, Saito H . Differential usage of three exons generates at least five different mRNAs encoding human leukocyte common antigens. J Exp Med. 1987; 166(5):1548-66. PMC: 2189669. DOI: 10.1084/jem.166.5.1548. View

Schon E, Jahn S, Kiessig S, Demuth H, Neubert K, Barth A . The role of dipeptidyl peptidase IV in human T lymphocyte activation. Inhibitors and antibodies against dipeptidyl peptidase IV suppress lymphocyte proliferation and immunoglobulin synthesis in vitro. Eur J Immunol. 1987; 17(12):1821-6. DOI: 10.1002/eji.1830171222. View

Kunkel T, Roberts J, Zakour R . Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987; 154:367-82. DOI: 10.1016/0076-6879(87)54085-x. View

Brenner S . The molecular evolution of genes and proteins: a tale of two serines. Nature. 1988; 334(6182):528-30. DOI: 10.1038/334528a0. View

10.

Schon E, Demuth H, EICHMANN E, Horst H, Korner I, Kopp J . Dipeptidyl peptidase IV in human T lymphocytes. Impaired induction of interleukin 2 and gamma interferon due to specific inhibition of dipeptidyl peptidase IV. Scand J Immunol. 1989; 29(2):127-32. DOI: 10.1111/j.1365-3083.1989.tb01108.x. View

11.

Heike M, Mobius U, Knuth A, Meuer S, Meyer zum Buschenfelde K . Tissue distribution of the T cell activation antigen Ta1. Serological, immunohistochemical and biochemical investigations. Clin Exp Immunol. 1988; 74(3):431-4. PMC: 1542019. View

12.

Mead D, Kemper B . Single-stranded DNA 'blue' T7 promoter plasmids: a versatile tandem promoter system for cloning and protein engineering. Protein Eng. 1986; 1(1):67-74. DOI: 10.1093/protein/1.1.67. View

13.

Hafler D, Chofflon M, Benjamin D, Dang N, Breitmeyer J . Mechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression. J Immunol. 1989; 142(8):2590-6. View

14.

Siekierka J, Staruch M, Hung S, Sigal N . FK-506, a potent novel immunosuppressive agent, binds to a cytosolic protein which is distinct from the cyclosporin A-binding protein, cyclophilin. J Immunol. 1989; 143(5):1580-3. View

15.

Morimoto C, Torimoto Y, Levinson G, Rudd C, Schrieber M, Dang N . 1F7, a novel cell surface molecule, involved in helper function of CD4 cells. J Immunol. 1989; 143(11):3430-9. View

16.

Dang N, Hafler D, Schlossman S, Breitmeyer J . FcR-mediated crosslinking of Ta1 (CDw26) induces human T lymphocyte activation. Cell Immunol. 1990; 125(1):42-57. DOI: 10.1016/0008-8749(90)90061-u. View

17.

Hegen M, Niedobitek G, Klein C, STEIN H, Fleischer B . The T cell triggering molecule Tp103 is associated with dipeptidyl aminopeptidase IV activity. J Immunol. 1990; 144(8):2908-14. View

18.

Ulmer A, Mattern T, Feller A, HEYMANN E, Flad H . CD26 antigen is a surface dipeptidyl peptidase IV (DPPIV) as characterized by monoclonal antibodies clone TII-19-4-7 and 4EL1C7. Scand J Immunol. 1990; 31(4):429-35. DOI: 10.1111/j.1365-3083.1990.tb02789.x. View

19.

Dang N, Torimoto Y, Deusch K, Schlossman S, Morimoto C . Comitogenic effect of solid-phase immobilized anti-1F7 on human CD4 T cell activation via CD3 and CD2 pathways. J Immunol. 1990; 144(11):4092-100. View

20.

Geppert T, Davis L, Gur H, Wacholtz M, Lipsky P . Accessory cell signals involved in T-cell activation. Immunol Rev. 1990; 117:5-66. DOI: 10.1111/j.1600-065x.1990.tb00566.x. View