The invasin protein of Yersinia spp. provides co-stimulatory activity to human T cells through interaction with beta 1 integrins.
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 beta 1 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 (EMBO J. 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 beta 1 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 beta 1 integrins. The proliferation induced by co-stimulation of CD4+ T cells was accompanied by the synthesis of the cytokines tumor necrosis factor-alpha and interferon-gamma, 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 TAKSKKFPSY 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.
Brett
S J
SJ
Department of Cell Biology, Wellcome Research Laboratories, Beckenham.
Mazurov
A V
AV
Charles
I G
IG
Tite
J P
JP
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D016023:Integrins; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015007:Yersinia / Q000276:immunology*
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D016827:CD8 Antigens; D016207:Cytokines; D016023:Integrins; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D011993:Recombinant Fusion Proteins; C053476:invasin, Yersinia