Specific inhibition of graft rejection by soluble MHC superdimers

Jonathan P Schneck, Joan Sechler, Sean M. O'Herrin, Joan G. Bieler, Nicholas Barnes, Amv Rosenberg

Research output: Contribution to journalArticle

Abstract

We have previously described a genetically engineered soluble divalent analog of an MHC molecule (soluble superdimer). This protein, H2Kb/IgG, was generated as a fusion protein between the extracellular domains of a murine class I polypeptide, H-2Kb, and an immunoglobulin heavy chain polypeptide. Soluble MHC superdimers inhibit lysis of target cells by alloreactive cytotoxic T cells at nanomolar concentrations. A direct binding assay showed high affinity binding, ICso of 1.2 nM, between the H-2Kb/IgG molecule and an H-2K"-specific alloreactive T cell clone. To analyze the influence of H-2Kb/IgG on in vivo responses, we have studied the effect of H-2Kb/IgG on skin graft rejection. Anti-H-2Kb specific responses were studied by engrafting skin from C57B1/6 mice (H2Kb) onto H-2Kbn" recipients. Median survival times increased by 7-10 days when animals were injected with H-2Kb/IgG, 500 ng/dose, every other day for a total of only six doses; several animals demonstrated long term graft survival, up to 60 days. There was no influence of H-2K"/IgG on graft rejection mediated by either a different class I MHC molecule, H2D , or by a full MHC mismatch. We are currently studying the mechanism of prolongation of graft survival using in vitro MLR derived from treated mice. These experiments demonstrate' selective in vivo immunosuppression of grafts rejection using soluble MHC superdimers. Thus soluble MHC superdimers effectively regulate in vivo allospecific immune responses.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996

Fingerprint

graft rejection
Graft Rejection
Grafts
Immunoglobulin G
skin (animal)
polypeptides
mice
T-lymphocytes
immunoglobulin heavy chains
T-cells
immunosuppression
Graft Survival
dosage
Molecules
animals
Skin
Animals
proteins
immune response
clones

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Schneck, J. P., Sechler, J., O'Herrin, S. M., Bieler, J. G., Barnes, N., & Rosenberg, A. (1996). Specific inhibition of graft rejection by soluble MHC superdimers. FASEB Journal, 10(6).

Specific inhibition of graft rejection by soluble MHC superdimers. / Schneck, Jonathan P; Sechler, Joan; O'Herrin, Sean M.; Bieler, Joan G.; Barnes, Nicholas; Rosenberg, Amv.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

Schneck, JP, Sechler, J, O'Herrin, SM, Bieler, JG, Barnes, N & Rosenberg, A 1996, 'Specific inhibition of graft rejection by soluble MHC superdimers', FASEB Journal, vol. 10, no. 6.
Schneck JP, Sechler J, O'Herrin SM, Bieler JG, Barnes N, Rosenberg A. Specific inhibition of graft rejection by soluble MHC superdimers. FASEB Journal. 1996;10(6).
Schneck, Jonathan P ; Sechler, Joan ; O'Herrin, Sean M. ; Bieler, Joan G. ; Barnes, Nicholas ; Rosenberg, Amv. / Specific inhibition of graft rejection by soluble MHC superdimers. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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