Open AccessA soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations.
Author(s) -
Joseph Dal Porto,
Teit E. Johansen,
Branimir Čatipović,
D J Parfiit,
David A. Tuveson,
Ulrik Gether,
Steven Kozlowski,
Douglas T. Fearon,
Jonathan P. Schneck
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.14.6671
Subject(s) - cytotoxic t cell , major histocompatibility complex , epitope , microbiology and biotechnology , biology , mhc class i , t cell , divalent , clone (java method) , antigen , chemistry , biochemistry , in vitro , immunology , immune system , gene , organic chemistry
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.