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Soluble pig lymphocyte activation gene-3 (LAG-3; CD223) inhibits human-to-pig xenogeneic mixed lymphocyte reaction

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Abstract

Lymphocyte activation gene-3 (LAG-3; CD223) is a transmembrane protein that is structurally similar to CD4. Since LAG-3 has a much higher binding affinity to MHC class II than that of CD4, several approaches using soluble LAG-3 were used to modulate immune responses by activation or inhibition of MHC class II expressing antigen presenting cells. In this study, we constructed soluble pig LAG-3 containing a critical binding site (D1 and D2 region) to MHC class II molecules, combined with a constant region of an immunoglobulin (Ig) heavy chain. Flow cytometry analyses indicated that soluble pig LAG-3 binds to both pig and human MHC class II molecules. Moreover, soluble pig LAG-3 can inhibit human lymphocyte proliferation in the human–pig xenogeneic mixed lymphocyte reaction in a dose-dependent manner. These results indicate that soluble pig LAG-3 may be useful for controlling the xenogeneic T cell immune responses between the human and pig.

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References

  • Andreae S, Buisson S, Triebel F (2003) MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223). Blood 102:2130–2137

    Article  CAS  PubMed  Google Scholar 

  • Buisson S, Triebel F (2005) LAG-3 (CD223) reduces macrophage and dendritic cell differentiation from monocyte precursors. Immunology 114:369–374

    Article  CAS  PubMed  Google Scholar 

  • Chun T, Byun HJ, Chung HY et al (2004) The effect of soluble LAG-3 (CD223) treatment in fetal thymic organ culture. Biotechnol Lett 26:1371–1377

    Article  CAS  PubMed  Google Scholar 

  • Di Carlo E, Cappello P, Sorrentino C et al (2005) Immunological mechanisms elicited at the tumor site by lymphocyte activation gene-3 (LAG-3) versus IL-12: sharing a common Th1 anti-tumor immune pathway. J Pathol 205:82–91

    Article  PubMed  Google Scholar 

  • Fougreray S, Brignone C, Triebel F (2006) A soluble LAG-3 protein as an immunopotentiator for therapeutic vaccines: Preclinical evaluation of IMP321. Vaccine 24:5426–5433

    Article  Google Scholar 

  • Huard B, Tournier M, Hercend T et al (1994) Lymphocyte-activation gene 3/major histocompatibility complex class II interaction modulates the antigenic response of CD4+ T lymphocytes. Eur J Immunol 24:3216–3221

    Article  CAS  PubMed  Google Scholar 

  • Huard B, Mastrangeli R, Prigent P et al (1997) Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc Natl Acad Sci USA 94:5744–5749

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi T, Taniguchi S, Neethling FA et al (1997) Delayed xenograft rejection of pig to baboon cardiac transplants after cobra venom factor therapy. Transplantation 64:1255–1261

    Article  CAS  PubMed  Google Scholar 

  • Lai L, Kolber-Simonds D, Park KW et al (2002) Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295:1089–1092

    Article  CAS  PubMed  Google Scholar 

  • Niemann H, Verhoeyen E, Wonigeit K et al (2001) Cytomegalovirus early promoter induced expression of hCD59 in porcine organs provides protection against hyperacute rejection. Transplantation 72:1898–1906

    Article  CAS  PubMed  Google Scholar 

  • Ory DS, Neugeboren BA, Mulligan RC (1996) A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes. Proc Natl Acad Sci USA 93:11400–11406

    Article  CAS  PubMed  Google Scholar 

  • Sprangers B, Water M, Billiau AD (2008) Xenotransplantation: where are we in 2008? Kidney Int 74:14–21

    Article  CAS  PubMed  Google Scholar 

  • Subramanyam M, Wands G, Nabioullin R et al (1998) Soluble human lymphocyte activation gene-3 modulates allospecific T cell responses. Int Immunol 10:679–689

    Article  CAS  PubMed  Google Scholar 

  • Triebel F, Jitsukawa S, Baixeras E et al (1990) LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med 1711:393–405

    Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Korea Health 21 R & D Project, Ministry of Health & Welfare, Republic of Korea (Project number: A040004).

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Correspondence to Taehoon Chun.

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Kim, SS., Byun, HJ., Kim, SH. et al. Soluble pig lymphocyte activation gene-3 (LAG-3; CD223) inhibits human-to-pig xenogeneic mixed lymphocyte reaction. Biotechnol Lett 32, 203–208 (2010). https://doi.org/10.1007/s10529-009-0144-9

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  • DOI: https://doi.org/10.1007/s10529-009-0144-9

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