INT149117

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Context Info
Confidence 0.52
First Reported 2003
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 31
Total Number 32
Disease Relevance 12.70
Pain Relevance 7.73

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

plasma membrane (CD80, CTLA4) Golgi apparatus (CTLA4) intracellular (CD80)
cell-cell signaling (CD80)
Anatomy Link Frequency
T-cell 11
CD86 9
hinge 2
plaque 2
regulatory T-cells 2
CD80 (Homo sapiens)
CTLA4 (Homo sapiens)
Pain Link Frequency Relevance Heat
abatacept 552 98.24 Very High Very High Very High
cytokine 362 97.08 Very High Very High Very High
psoriasis 420 96.12 Very High Very High Very High
rheumatoid arthritis 480 95.84 Very High Very High Very High
Arthritis 484 87.80 High High
tolerance 93 86.40 High High
Pain 18 84.68 Quite High
Inflammation 346 77.56 Quite High
metalloproteinase 11 74.96 Quite High
adenocard 3 74.60 Quite High
Disease Link Frequency Relevance Heat
Psoriasis 470 96.12 Very High Very High Very High
Rheumatoid Arthritis 481 95.84 Very High Very High Very High
Autoimmune Disease 110 95.24 Very High Very High Very High
Cancer 544 93.20 High High
Apoptosis 41 93.08 High High
Seronegative Spondarthritis 118 87.80 High High
Skin Cancer 239 87.36 High High
Graft Vs Host Disease 23 86.56 High High
Organ Transplantation 12 85.48 High High
Leukocytosis 5 85.08 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
CTLA-4 binds to CD80 and CD86 with higher avidity than CD28, thus preventing co-stimulation through this pathway, and is a major down-regulatory signal for T cells.
CD80 Binding (binds) of CTLA-4 in CD86
1) Confidence 0.52 Published 2008 Journal Annals of the Rheumatic Diseases Section Body Doc Link PMC2569144 Disease Relevance 0.52 Pain Relevance 0.50
The most important ligand is CTLA-4, a well-defined down-regulator of T-cell activation, which has a much higher binding affinity for CD80/CD86 than CD28.
CD80 Binding (affinity) of CTLA-4 in T-cell
2) Confidence 0.43 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727897 Disease Relevance 0.36 Pain Relevance 0.67
CTLA-4 is a regulator of co-stimulation and inhibits the activation of T cells through interfering with the interaction of CD80/86 on antigen-presenting cells with CD28 on T cells.
CD80 Binding (interaction) of CTLA-4 in T cells
3) Confidence 0.29 Published 2008 Journal Ann. Rheum. Dis. Section Abstract Doc Link 18203760 Disease Relevance 0.13 Pain Relevance 0
Thus, in abatacept, a series of directed cysteine to serine mutations were introduced in the hinge region to reduce this Fc- mediated binding.21 Although abatacept proved to be highly efficacious for autoimmune T cell-mediated autoimmune disorders, such as rheumatoid arthritis and psoriasis, it was found to be an inadequate maintenance immunosuppressive agent in nonhuman primate models of transplantation.22–24 Studies into potential reasons for this disconnect found that although CTLA4 binds with a much higher avidity to CD80 and CD86 than does CD28, CTLA4-Ig was significantly less potent at inhibiting CD86-dependent as opposed to CD80-dependent costimulation.25
CD80 Binding (binds) of CTLA4 in hinge associated with psoriasis, autoimmune disease, rheumatoid arthritis and abatacept
4) Confidence 0.25 Published 2010 Journal Drug Design, Development and Therapy Section Body Doc Link PMC2998809 Disease Relevance 0.29 Pain Relevance 0.39
CTLA-4 has a higher receptor affinity for both B7-1 and B7-2 than CD28.
B7 Binding (affinity) of CTLA-4
5) Confidence 0.23 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721321 Disease Relevance 0.05 Pain Relevance 0
CTLA-4, when binding to B7, may activate the immunosuppressive pathway of tryptophan catabolism in DCs (Grohmann et al 2002).
B7 Binding (binding) of CTLA-4
6) Confidence 0.23 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721321 Disease Relevance 0.07 Pain Relevance 0
CTLA-4 has a higher receptor affinity for both B7-1 and B7-2 than CD28.
B7 Binding (affinity) of CTLA-4
7) Confidence 0.23 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721321 Disease Relevance 0.05 Pain Relevance 0
This led to the development of belatacept, a second-generation CTLA4-Ig that exhibits superior binding to CD80 and CD86 as compared with the parent CTLA4-Ig.


CD80 Binding (binding) of CTLA4-Ig in CD86
8) Confidence 0.21 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2582812 Disease Relevance 1.21 Pain Relevance 0.76
Thus, in abatacept, a series of directed cysteine to serine mutations were introduced in the hinge region to reduce this Fc- mediated binding.21 Although abatacept proved to be highly efficacious for autoimmune T cell-mediated autoimmune disorders, such as rheumatoid arthritis and psoriasis, it was found to be an inadequate maintenance immunosuppressive agent in nonhuman primate models of transplantation.22–24 Studies into potential reasons for this disconnect found that although CTLA4 binds with a much higher avidity to CD80 and CD86 than does CD28, CTLA4-Ig was significantly less potent at inhibiting CD86-dependent as opposed to CD80-dependent costimulation.25
CD80 Binding (binds) of CTLA4-Ig in hinge associated with psoriasis, autoimmune disease, rheumatoid arthritis and abatacept
9) Confidence 0.19 Published 2010 Journal Drug Design, Development and Therapy Section Body Doc Link PMC2998809 Disease Relevance 0.29 Pain Relevance 0.39
Like native CTLA4, the fusion protein binds more avidly to CD80/86 than to CD28.
CD80 Binding (binds) of CTLA4
10) Confidence 0.19 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2582812 Disease Relevance 0.54 Pain Relevance 0.20
B7/CTLA-4 interactions and regulatory T-cells
B7 Binding (interactions) of CTLA-4 in regulatory T-cells
11) Confidence 0.17 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721321 Disease Relevance 0.06 Pain Relevance 0.18
B7/CTLA-4 interactions and regulatory T-cells
B7 Binding (interactions) of CTLA-4 in regulatory T-cells
12) Confidence 0.17 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721321 Disease Relevance 0.06 Pain Relevance 0.18
Because CD152 has a high affinity for CD80 and CD86, soluble forms of CTLA4 inhibit the interaction of CD28 with its ligands.
CD80 Binding (affinity) of CTLA4 in CD86
13) Confidence 0.16 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC2833981 Disease Relevance 0.77 Pain Relevance 0.32
Preferential engagement of CTLA-4, instead of CD28, with CD80/CD86 may provide a negative proliferative signal [78].
CD80 Binding (engagement) of CTLA-4 in CD86
14) Confidence 0.16 Published 2008 Journal Pediatr Rheumatol Online J Section Body Doc Link PMC2633304 Disease Relevance 0 Pain Relevance 0.04
Wing et al. described the role of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a protein highly expressed by Tregs, which inhibits the immune response [39]; CTLA-4 binds the costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with higher affinity than CD28, inhibiting the second signal, necessary to immune activation [40].
CD80 Binding (binds) of CTLA-4 in cytotoxic T-lymphocyte
15) Confidence 0.15 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.43 Pain Relevance 0.23
CTLA-4, a natural inhibitor of CD28, binds to CD80/86 molecules with high affinity and competes with CD28.
CD80 Binding (binds) of CTLA-4
16) Confidence 0.14 Published 2005 Journal J Immune Based Ther Vaccines Section Body Doc Link PMC1208938 Disease Relevance 0.75 Pain Relevance 0.32
Because CD152 has a high affinity for CD80 and CD86, soluble forms of CTLA4 inhibit the interaction of CD28 with its ligands.
CD80 Binding (affinity) of CD152 in CD86
17) Confidence 0.13 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC2833981 Disease Relevance 0.81 Pain Relevance 0.31
Because CD152 has a high affinity for CD80 and CD86, soluble forms of CTLA4 inhibit the interaction of CD28 with its ligands.
CD80 Binding (affinity) of CTLA4 in CD86
18) Confidence 0.12 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC2833981 Disease Relevance 0.77 Pain Relevance 0.32
Cytotoxic T-cell Lymphocyte Antigen-4 (CTLA4) bears structural similarity to CD28, but has much higher affinity for CD80 and CD86 (Bluestone et al 2006).
CD80 Binding (affinity) of T-cell Lymphocyte Antigen-4 in CD86
19) Confidence 0.11 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721362 Disease Relevance 0.64 Pain Relevance 0.63
Cytotoxic T-cell Lymphocyte Antigen-4 (CTLA4) bears structural similarity to CD28, but has much higher affinity for CD80 and CD86 (Bluestone et al 2006).
CD80 Binding (affinity) of CTLA4 in CD86
20) Confidence 0.11 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721362 Disease Relevance 0.58 Pain Relevance 0.63

General Comments

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