A Soluble Multimeric Recombinant CD2 Protein Identifies CD48 As a Low Affinity Ligand for Human CD2: Divergence of CD2 Ligands During the Evolution of Humans and Mice

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1993 May 1

PMID 7683037

Citations 41

Authors

A R Arulanandam

P Moingeon

M F Concino

M A Recny

K Kato

H Yagita

S Koyasu

E L Reinherz

Affiliations

Soon will be listed here.

Abstract

To search for possible ligands of CD2 distinct from CD58 (lymphocyte function-associated antigen 3), we have produced a soluble pentameric CD2-immunoglobulin (Ig) fusion protein (spCD2) linking the 182-amino acid human CD2 extracellular segment with CH2-CH3-CH4 domains of human IgM heavy chain, thus enhancing the micromolar affinity of the CD2 monomer through multimeric interaction. Using quantitative immunofluorescence and standard stringency wash conditions, we observed that the binding of spCD2 to human B lymphoblastoid JY cells and red blood cells is virtually inhibited by anti-CD58 TS2/9 monoclonal antibody, even though these cells express levels of CD48 and CD59 comparable to CD58. Consistent with these results, spCD2 did not show any binding to Chinese hamster ovary (CHO) cells transfected with human CD48 or CD59. However, binding studies on CD48-, CD58-, or CD59-transfected CHO cells with spCD2 under low stringency wash conditions revealed that human CD48 is a low affinity ligand of human CD2 compared with CD58 (Kd approximately 10(-4) vs. approximately 10(-6) M, respectively). The findings are noteworthy given that in the murine system CD48 is the major ligand for CD2. No detectable binding was observed to CD59-transfected CHO cells despite a report suggesting that CD59 may bind to the human CD2 adhesion domain. Importantly, in cell-cell adhesion assays between CD2+ Jurkat T cells and CD48- or CD59-transfected CHO cells, there was no conjugate formation, whereas binding of Jurkat T cells to CD58-transfected CHO cells was readily detected. Collectively, our findings provide evidence for a conservation of the CD2-CD48 interaction in the human species that may be of limited, if any, functional significance. Given the importance of the CD2-CD48 interaction in the murine system and CD2-CD58 interaction in humans, it would appear that there has been a divergence of functional CD2 ligands during the evolution of humans and mice.

Citing Articles

Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2.

Jo Y, Sim H, Yun B, Park Y, Jin H Exp Mol Med. 2024; 56(10):2113-2126.

PMID: 39349829 PMC: 11541569. DOI: 10.1038/s12276-024-01317-9.

The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity.

Ho P, Melms J, Rogava M, Frangieh C, Pozniak J, Shah S Cancer Cell. 2023; 41(7):1207-1221.e12.

PMID: 37327789 PMC: 10524902. DOI: 10.1016/j.ccell.2023.05.014.

CD59-Regulated Ras Compartmentalization Orchestrates Antitumor T-cell Immunity.

Li L, Ding P, Lv X, Xie S, Li L, Chen J Cancer Immunol Res. 2022; 10(12):1475-1489.

PMID: 36206575 PMC: 9716252. DOI: 10.1158/2326-6066.CIR-21-1072.

The interplay between membrane topology and mechanical forces in regulating T cell receptor activity.

Al-Aghbar M, Jainarayanan A, Dustin M, Roffler S Commun Biol. 2022; 5(1):40.

PMID: 35017678 PMC: 8752658. DOI: 10.1038/s42003-021-02995-1.

CD48-expressing non-small-cell lung cancer cells are susceptible to natural killer cell-mediated cytotoxicity.

Park E, Won Jun H, Ho Na I, Lee H, Yun J, Kim H Arch Pharm Res. 2021; 45(1):1-10.

PMID: 34905179 DOI: 10.1007/s12272-021-01365-z.

References

Luo W, van de Velde H, von Hoegen I, Parnes J, Thielemans K . Ly-1 (CD5), a membrane glycoprotein of mouse T lymphocytes and a subset of B cells, is a natural ligand of the B cell surface protein Lyb-2 (CD72). J Immunol. 1992; 148(6):1630-4. View

de Fougerolles A, Springer T . Intercellular adhesion molecule 3, a third adhesion counter-receptor for lymphocyte function-associated molecule 1 on resting lymphocytes. J Exp Med. 1992; 175(1):185-90. PMC: 2119096. DOI: 10.1084/jem.175.1.185. View

Kato K, Koyanagi M, Okada H, Takanashi T, Wong Y, Williams A . CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation. J Exp Med. 1992; 176(5):1241-9. PMC: 2119417. DOI: 10.1084/jem.176.5.1241. View

Killeen N, Stuart S, Littman D . Development and function of T cells in mice with a disrupted CD2 gene. EMBO J. 1992; 11(12):4329-36. PMC: 557006. DOI: 10.1002/j.1460-2075.1992.tb05532.x. View

Deckert M, Kubar J, Zoccola D, Angelisova P, Horejsi V, Bernard A . CD59 molecule: a second ligand for CD2 in T cell adhesion. Eur J Immunol. 1992; 22(11):2943-7. DOI: 10.1002/eji.1830221128. View

Recny M, Luther M, Knoppers M, Neidhardt E, Khandekar S, Concino M . N-glycosylation is required for human CD2 immunoadhesion functions. J Biol Chem. 1992; 267(31):22428-34. View

Subramani S, Mulligan R, Berg P . Expression of the mouse dihydrofolate reductase complementary deoxyribonucleic acid in simian virus 40 vectors. Mol Cell Biol. 1981; 1(9):854-64. PMC: 369369. DOI: 10.1128/mcb.1.9.854-864.1981. View

Marlin S, Springer T . Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell. 1987; 51(5):813-9. DOI: 10.1016/0092-8674(87)90104-8. View

Sanchez-Madrid F, Krensky A, Ware C, Robbins E, Strominger J, Burakoff S . 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; 79(23):7489-93. PMC: 347365. DOI: 10.1073/pnas.79.23.7489. View

10.

Krensky A, Sanchez-Madrid F, Robbins E, Nagy J, Springer T, Burakoff S . The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: cell surface antigens associated with CTL-target interactions. J Immunol. 1983; 131(2):611-6. View

11.

Meuer S, Hussey R, Fabbi M, Fox D, Acuto O, Fitzgerald K . An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984; 36(4):897-906. DOI: 10.1016/0092-8674(84)90039-4. View

12.

Boulianne G, Hozumi N, Shulman M . Production of functional chimaeric mouse/human antibody. Nature. 1984; 312(5995):643-6. DOI: 10.1038/312643a0. View

13.

Siliciano R, Pratt J, Schmidt R, Ritz J, Reinherz E . Activation of cytolytic T lymphocyte and natural killer cell function through the T11 sheep erythrocyte binding protein. Nature. 1985; 317(6036):428-30. DOI: 10.1038/317428a0. View

14.

Vollger L, Tuck D, Springer T, Haynes B, Singer K . Thymocyte binding to human thymic epithelial cells is inhibited by monoclonal antibodies to CD-2 and LFA-3 antigens. J Immunol. 1987; 138(2):358-63. View

15.

Hunig T, Tiefenthaler G, Meyer zum Buschenfelde K, Meuer S . Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand. Nature. 1987; 326(6110):298-301. DOI: 10.1038/326298a0. View

16.

Selvaraj P, Plunkett M, Dustin M, Sanders M, Shaw S, Springer T . The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3. Nature. 1987; 326(6111):400-3. DOI: 10.1038/326400a0. View

17.

Springer T, Dustin M, Kishimoto T, Marlin S . The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol. 1987; 5:223-52. DOI: 10.1146/annurev.iy.05.040187.001255. View

18.

Clayton L, Sayre P, Novotny J, Reinherz E . Murine and human T11 (CD2) cDNA sequences suggest a common signal transduction mechanism. Eur J Immunol. 1987; 17(9):1367-70. DOI: 10.1002/eji.1830170922. View

19.

Seed B . An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2. Nature. 1987; 329(6142):840-2. DOI: 10.1038/329840a0. View

20.

Doyle C, Strominger J . Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987; 330(6145):256-9. DOI: 10.1038/330256a0. View