A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations

Joseph Dal Porto, Teit Eliot Johansen, Branimir Čatipović, Donna Jo Parfiit, Dave Tuveson, Ulrik Gether, Steve Kozlowski, Douglas T. Fearon, Jonathan P Schneck

Research output: Contribution to journalArticle

Abstract

Genetically engineered or chemically purified soluble monovalent major histocompatibility complex (MHC) molecules, which have previously been used to study T cells, have not blocked cytotoxic T-cell responses. Here we describe a genetically engineered divalent class I MHC molecule which inhibits lysis of target cells by alloreactive cytotoxic T cells. This protein, H-2Kb/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. The chimeric protein has serological and biochemical characteristics of both the MHC and IgG polypeptides. Nanomolar concentrations of H-2Kb/IgG inhibited lysis of H-2Kb-expressing target cells not only by alloreactive H-2Kb-specific T-cell clones but also by alloreactive H-2Kb-specific primary T-cell cultures. A direct binding assay showed high-affinity binding between the H-2Kb/IgG molecule and an H-2Kb-specific alloreactive T-cell clone. Unlabeled H-2Kb/IgG displaced 125I-labeled H-2Kb/IgG from T cells with an IC50 of 1.2 nM.

Original languageEnglish (US)
Pages (from-to)6671-6675
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number14
StatePublished - Jul 15 1993

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Major Histocompatibility Complex
T-Lymphocytes
Immunoglobulin G
Peptides
Clone Cells
Immunoglobulin Heavy Chains
Proteins
Primary Cell Culture
Inhibitory Concentration 50

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations. / Dal Porto, Joseph; Johansen, Teit Eliot; Čatipović, Branimir; Parfiit, Donna Jo; Tuveson, Dave; Gether, Ulrik; Kozlowski, Steve; Fearon, Douglas T.; Schneck, Jonathan P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 14, 15.07.1993, p. 6671-6675.

Research output: Contribution to journalArticle

Dal Porto, J, Johansen, TE, Čatipović, B, Parfiit, DJ, Tuveson, D, Gether, U, Kozlowski, S, Fearon, DT & Schneck, JP 1993, 'A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations', Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 14, pp. 6671-6675.
Dal Porto, Joseph ; Johansen, Teit Eliot ; Čatipović, Branimir ; Parfiit, Donna Jo ; Tuveson, Dave ; Gether, Ulrik ; Kozlowski, Steve ; Fearon, Douglas T. ; Schneck, Jonathan P. / A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations. In: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; Vol. 90, No. 14. pp. 6671-6675.
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