The invasin protein of Yersinia spp. provides co‐stimulatory activity to human T cells through interaction with β integrins

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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.