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A synthetic random basic copolymer with promiscuous binding to class II major histocompatibility complex molecules inhibits T-cell proliferative responses to major and minor histocompatibility antigens in vitro and confers the capacity to prevent murine graft-versus-host disease in vivo.

Publication ,  Journal Article
Schlegel, PG; Aharoni, R; Chen, Y; Chen, J; Teitelbaum, D; Arnon, R; Sela, M; Chao, NJ
Published in: Proc Natl Acad Sci U S A
May 14, 1996

Graft-versus-host disease (GVHD) is a T-cell-mediated disease of transplanted donor T cells recognizing host alloantigens. Data presented in this report show, to our knowledge, for the first time that a synthetic copolymer of the amino acids L-Glu, L-Lys, L-Ala, and L-Tyr (molecular ratio, 1.9:6.0:4.7:1.0; Mr, 6000-8500) [corrected], termed GLAT, with promiscuous binding to multiple major histocompatibility complex class II alleles is capable of preventing lethal GVHD in the B10.D2 --> BALB/c model (both H-2d) across minor histocompatibility barriers. Administration of GLAT over a limited time after transplant significantly reduced the incidence, onset, and severity of disease. GLAT also improved long-term survival from lethal GVHD: 14/25 (56%) of experimental mice survived > 140 days after transplant compared to 2/26 of saline-treated or to 1/10 of hen egg lysozyme-treated control mice (P < 0.01). Long-term survivors were documented to be fully chimeric by PCR analysis of a polymorphic microsatellite region in the interleukin 1beta gene. In vitro, GLAT inhibited the mixed lymphocyte culture in a dose-dependent fashion across a variety of major barriers tested. Furthermore, GLAT inhibited the response of nylon wool-enriched T cells to syngeneic antigen-presenting cells presenting minor histocompatibility antigens. Prepulsing of the antigen-presenting cells with GLAT reduced the proliferative response, suggesting that GLAT inhibits antigen presentation.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 14, 1996

Volume

93

Issue

10

Start / End Page

5061 / 5066

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Protein Binding
  • Polymers
  • Peptides
  • Molecular Sequence Data
  • Minor Histocompatibility Antigens
  • Mice, Inbred CBA
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
 

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Schlegel, P. G., R. Aharoni, Y. Chen, J. Chen, D. Teitelbaum, R. Arnon, M. Sela, and N. J. Chao. “A synthetic random basic copolymer with promiscuous binding to class II major histocompatibility complex molecules inhibits T-cell proliferative responses to major and minor histocompatibility antigens in vitro and confers the capacity to prevent murine graft-versus-host disease in vivo.Proc Natl Acad Sci U S A 93, no. 10 (May 14, 1996): 5061–66. https://doi.org/10.1073/pnas.93.10.5061.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 14, 1996

Volume

93

Issue

10

Start / End Page

5061 / 5066

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Protein Binding
  • Polymers
  • Peptides
  • Molecular Sequence Data
  • Minor Histocompatibility Antigens
  • Mice, Inbred CBA
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice