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The invasin protein of Yersinia spp. provides co‐stimulatory activity to human T cells through interaction with β integrins
Author(s) -
Brett Sara J.,
Mazurov Alexey V.,
Charles Ian G.,
Tite John P.
Publication year - 1993
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830230732
Subject(s) - integrin , biology , yersinia pseudotuberculosis , yersinia , t cell , cytotoxic t cell , microbiology and biotechnology , biochemistry , cell , bacteria , immune system , in vitro , immunology , genetics , virulence , gene
Abstract The invasin proteins of Yersinia spp . are outer membrane proteins which are involved in the penetration of these bacteria into mammalian cells (Cell 1990. 60 : 861). Invasin binds to several different β integrins with extremely high affinity, the integrin‐binding domain of invasin has been mapped to the C‐terminal 192 amino‐acids of the molecule ( J . Biol. Chem . 1991.266:24367). Expression of this fragment alone on the cell surface of non‐invasive bacteria is enough to confer the invasive phenotype on these strains (EMBOJ . 1990. 9 :1979). Here we show that the carboxy‐terminal 192 amino acids of invasin expressed as a fusion protein with the maltose binding protein of E. coli is capable of delivering co‐stimulatory signals to human T cells through the β integrins. Co‐stimulation was assayed by the ability of invasin to augment the response of highly purified CD4 + and CD8 + T cells to co‐immobilized anti‐CD3 antibody. Antibody blocking studies indicated that the co‐stimulation was mediated through β integrins. The proliferation induced by co‐stimulation of CD4 + T cells was accompanied by the synthesis of the cytokines tumor necrosis factor‐a and interferon‐y, whereas the activation of CD8 + T cells led to the generation of cytotoxic effectors. The region of the invasin molecule involved in T cell activation was further mapped using synthetic peptides. A region of the invasin molecule containing the residues TAKSKKFP‐SY could substitute for invasin in T cell activation. The co‐stimulation by peptide could also be inhibited by anti‐integrin antibodies. The observation that an outer membrane protein of a bacterium which is associated with reactive arthritis and other autoimmune spondyloarthropathies can act as a T cell co‐stimulus may have implications for the etiology of these diseases.