Evidence for diversity within Propionibacterium acnes: a comparison of the T-cell stimulatory activity of isolates from inflammatory acne, endocarditis and the laboratory

2004 ◽  
Vol 18 (4) ◽  
pp. 450-454 ◽  
Author(s):  
U Jappe ◽  
R Boit ◽  
MD Farrar ◽  
E Ingham ◽  
J Sandoe ◽  
...  
Keyword(s):  
T Cell ◽  
Propionibacterium Acnes ◽  
Stimulatory Activity

scholarly journals Variable expression of immunoreactive surface proteins of Propionibacterium acnes

Microbiology ◽  
2006 ◽  
Vol 152 (12) ◽  
pp. 3667-3681 ◽  
Author(s):  
Michael J. Lodes ◽  
Heather Secrist ◽  
Darin R. Benson ◽  
Shyian Jen ◽  
Kurt D. Shanebeck ◽  
...  
Keyword(s):  
T Cell ◽  
Propionibacterium Acnes ◽  
Cell Epitope ◽  
Terminal Region ◽  
Clinical Isolates ◽  
Carboxy Terminus ◽  
Dermatan Sulphate ◽  
Variable Expression ◽  
Lpxtg Motif ◽  
Amino Terminal

Despite accumulating data implicating Propionibacterium acnes in a variety of diseases, its precise role in infection remains to be determined. P. acnes antigen-specific CD4+ T cells are present in early inflamed acne lesions and may be involved in the inflammatory response; however, little is known about the specific antigens involved. In this study, B cell and T cell antigens from P. acnes expression libraries were cloned and evaluated and the four predominant proteins identified were investigated. Two of these antigens share some homology with an M-like protein of Streptococcus equi and have dermatan-sulphate-binding activity (PA-25957 and 5541). The remaining two antigens, PA-21693 and 4687, are similar to the product of the Corynebacterium diphtheriae htaA gene from the hmu ABC transport locus, although only one of these (PA-21693) is encoded within an hmu-like operon and conserved amongst a range of clinical isolates. All four proteins contain an LPXTG motif, although only PA-21693 contains a characteristic sortase-sorting signal. Variation in the expression of PA-4687, 25957 and 5541 is evident amongst clinical isolates and is generated both by frameshifts associated with the putative signal peptide and by variable numbers of repeat regions toward the carboxy-terminus, potentially generating heterogeneity of molecular mass and antigenic variation. In addition, in the case of PA-25957, a frameshift in a C-rich region at the extreme carboxy-terminus eliminates the LPXTG motif in some isolates. For the dermatan-sulphate-binding PA-25957, IgG1 antibody in serum from acne-positive donors was shown to be specific for the amino-terminal region of the protein, which also contains a CD4+ T cell epitope. In contrast, serum from acne-negative donors shows an IgG2 and IgG3 antibody subclass response to the carboxy-terminal region. These data have implications for the potential role of P. acnes in inflammatory acne and other diseases.

T-cell stimulatory activity of liver and spleen dendritic cell during a murine model of hepatocarcinogenesis

2007 ◽  
Vol 39 (3) ◽  
pp. A16
Author(s):  
A. Castellaneta ◽  
Leo Di ◽  
N. De Tullio ◽  
F. Gagliardi ◽  
A. Amoruso ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Murine Model ◽  
Stimulatory Activity

scholarly journals The co-stimulatory activity of Tim-3 requires Akt and MAPK signaling and immune synapse recruitment

2019 ◽  
Author(s):  
Shunsuke Kataoka ◽  
Priyanka Manandhar ◽  
Creg J. Workman ◽  
Hridesh Banerjee ◽  
Andrea L. Szymczak-Workman ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Mapk Signaling ◽  
Immune Synapse ◽  
Downstream Signaling ◽  
Stimulatory Activity

AbstractExpression of the transmembrane protein Tim-3 is increased on dysregulated T cells undergoing chronic T cell activation, including in chronic infection and solid tumors. We and others previously reported that Tim-3 exerts apparently paradoxical co-stimulatory activity in T cells (and other cells), including enhancement of ribosomal S6 protein phosphorylation (pS6). Here we examined the upstream signaling pathways that control Tim3-mediated increases in pS6 in T cells. We have also defined the localization of Tim-3 relative to the T cell immune synapse and impacts on downstream signaling. Recruitment of Tim-3 to the immune synapse was regulated exclusively by the transmembrane domain, replacement of which impaired Tim-3 co-stimulation of pS6. Strikingly, enforced localization of the Tim-3 cytoplasmic domain to the immune synapse in the context of a chimeric antigen receptor still allowed for robust T cell activation. Our findings are consistent with a model whereby Tim-3 enhances TCR-proximal signaling under acute conditions.

scholarly journals Mutational Analysis of Superantigen Activity Responsible for the Induction of Skin Erythema by Streptococcal Pyrogenic Exotoxin C

1998 ◽  
Vol 66 (10) ◽  
pp. 5020-5026 ◽  
Author(s):  
Junichi Yamaoka ◽  
Eijiro Nakamura ◽  
Yoshifumi Takeda ◽  
Sadao Imamura ◽  
Nagahiro Minato
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mutational Analysis ◽  
Wild Type ◽  
Stimulatory Activity ◽  
Fold Reduction ◽  
Skin Erythema ◽  
Dose Dependent Fashion

ABSTRACT Streptococcal pyrogenic exotoxin C (SPEC), when injected intradermally, induces erythema in unsensitized rabbits. In the present study, we examined whether this erythema induction is due to the T-cell stimulatory activity of SPEC as a superantigen. Analysis by using single-residue mutant SPECs indicated that mutant SPECs Y15I, A16E, and Y17I, in which tyrosine 15, alanine 16, and tyrosine 17 were replaced with isoleucine, glutamic acid, and isoleucine, respectively, exhibited significantly reduced mitogenic activity for Vβ2+ human T cells in vitro, and Y15I showed as much as a 1,000-fold reduction. Y15I mutant SPEC, however, retained the ability to bind to major histocompatibility complex class II antigen and to form a homodimer, implying that residue 15 is critically important for the interaction of SPEC with T-cell antigen receptor β chains. When injected intradermally into normal rabbits, wild-type SPEC induced a characteristic erythema after 3 h in a dose-dependent fashion, which was associated with polymorphonuclear and mononuclear cell infiltration. This erythema formation was found to be severely suppressed by systemic pretreatment with cyclosporin A, suggesting the involvement of host T cells. Y15I mutant SPEC exhibited nearly 1,000-fold less erythema induction in vivo than wild-type SPEC. Altogether, the present results strongly suggest that erythema induction in rabbits by SPEC is attributable mostly to its T-cell stimulatory activity as a superantigen.

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