{"id":2465,"date":"2017-04-25T09:11:02","date_gmt":"2017-04-25T09:11:02","guid":{"rendered":"http:\/\/www.caltagmedsystems.co.uk\/information\/?p=2465"},"modified":"2022-06-21T15:25:02","modified_gmt":"2022-06-21T15:25:02","slug":"t-cell-activation-the-purpose-of-cd28-ctla-4-and-cd80cd86","status":"publish","type":"post","link":"https:\/\/www.caltagmedsystems.co.uk\/information\/t-cell-activation-the-purpose-of-cd28-ctla-4-and-cd80cd86\/","title":{"rendered":"T-cell Activation: The Purpose of CD28, CTLA-4, and CD80\/CD86"},"content":{"rendered":"

A Guide to CD28, CTLA-4, and CD80\/CD86 Interaction and Signaling<\/strong><\/p>\n

Immune checkpoint receptors like CD28 and CTLA-4 have been of great interest in the research of cancer immunotherapy. These receptors and their ligands are part of what regulates T-cell activation by antigen presenting cells (APCs) and the immune system\u2019s ability to target cancerous cells. This blog will serve as an outline of possible outcomes of T-cell regulation based on the interactions of T-cell receptors, CD28, CTLA-4, and their ligands CD80 and CD86.<\/p>\n

Receptors<\/strong><\/p>\n

 <\/p>\n

T-<\/em>cell Receptor (TCR):<\/em><\/p>\n

Activation of the TCR<\/a> and MHC:Antigen complex is imperative for eliciting an immune response. Although the TCR can receive a signal and elicit a response on its own, it typically requires co-stimulation of another surface receptor to bolster the signal and elicit a response. Without co-stimulation, the cell will either become anergic, i.e., it will not activate, or it will undergo apoptosis.<\/p>\n

 <\/p>\n

CD28 Receptor:<\/em><\/p>\n

The CD28<\/a> surface receptor is presented on na\u00efve T-cells, and is important for co-stimulation with the TCR. CD28 can be bound by the ligands CD80 and CD86 (B7-1 and B7-2) presented by APCs. If the TCR binds a target without CD28 binding one of these two ligands, co-stimulation will not occur, and the T-cell will be anergic. CD28 is also expressed in high concentration, but is a low affinity receptor. This is important to keep in mind because of the competitive binding posed by CTLA-4.<\/p>\n

 <\/p>\n

CTLA-4 Receptor:<\/em><\/p>\n

While CD28<\/a> leads to activation of the T-cell when it binds CD80 or CD86, CTLA-4 deactivates the TCR when it stimulated by CD80 or CD86 ligands, leading to either anergy or apoptosis. This makes CTLA-4 potentially dangerous in the case of cancer and other diseases: upregulation can lead to desensitization of T-cells to CD80\/CD86 presenting APCs, preventing the T-cell from eliciting an immune response when it is necessary. Additionally, CTLA-4 can be expressed in a soluble form, creating binding interference between CD80\/CD86 and CD28 and further inhibiting T-cell activation.<\/p>\n

 <\/p>\n

Antigen Presenting Cell Ligands<\/strong><\/p>\n

 <\/p>\n

MHC:Antigen(Ag) Complex:<\/em><\/p>\n

The MHC:Ag complex is the ligand used by APCs to signal T-cell through the TCR to elicit an immune response. The MHC presents a peptide fragment from a foreign molecule for the TCR to recognize. If signaling is successful, the T-cell will be activated and perform its specific function to create the immune response. This will still require co-stimulation of an appropriate surface receptor such as CD28 to complete activation.<\/p>\n

 <\/p>\n

CD80 (B7-1):<\/em><\/p>\n

CD80<\/a> is capable of binding both CD28 and CTLA-4. This ligand is expressed by APCs, and serves as one of the co-stimulatory molecules of T-cell activation. CD80 has a greater affinity for CTLA-4 over CD28. [1]<\/sup><\/a> Higher CD80 concentrations in the immunological synapse are responsible for recruiting greater amounts of CTLA-4 than CD28.[2]<\/sup><\/a> Together, these lead us to believe that greater concentrations of CD80 over CD86 can more often lead to anergy or apoptosis.<\/p>\n

 <\/p>\n

CD86 (B7-2):<\/em><\/p>\n

CD86<\/a> is a homolog of CD80 that binds the exact same receptors. In contrast with CD80, CD86 is associated more with successful co-stimulation of the TCR, while CD80 is often more inhibitory. This is due to earlier and more abundant expression patterns of CD86 in APCs.[2]<\/sup><\/a><\/p>\n

 <\/p>\n

The Big Picture<\/strong><\/p>\n

When a T-cell encounters an antigen presenting cell, an immunological synapse is formed where the signaling between the two cells will take place. For successful signaling, the T-cell receptor must bind the MHC, and a co-stimulatory molecule such as CD28 must be bound by CD80\/CD86. CTLA-4 is also presented on the surface of a T-cell, and competitively binds CD80\/CD86 with higher affinity to create an inhibitory signal. If CTLA-4 signaling outweighs CD28 signaling, the T-cell will become anergic or undergo apoptosis. APCs presenting larger amounts of CD80 are perceived to be more likely to recruit CTLA-4 resulting in inhibition of T-cell activation, while those presenting larger amounts of CD86 will more effectively bind CD28 and stimulate T-cell activation and immune response.<\/p>\n

 <\/p>\n

 <\/p>\n

Originally posted by ProSci<\/a><\/p>\n

  Find out how ProSci can help your Antibody needs today!<\/a><\/p>\n

 <\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

A Guide to CD28, CTLA-4, and CD80\/CD86 Interaction and Signaling Immune checkpoint receptors like CD28 and CTLA-4 have been of great interest in the research of cancer immunotherapy. These receptors and their ligands are part of what regulates T-cell activation<\/p>\n","protected":false},"author":13,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[132],"tags":[7,256,257,258,259,50,158,77],"class_list":["post-2465","post","type-post","status-publish","format-standard","hentry","category-antibodies","tag-cancer","tag-cd28","tag-cd80","tag-cd86","tag-ctla-4","tag-immunology","tag-immunotherapy","tag-prosci"],"_links":{"self":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts\/2465","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/comments?post=2465"}],"version-history":[{"count":8,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts\/2465\/revisions"}],"predecessor-version":[{"id":6744,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts\/2465\/revisions\/6744"}],"wp:attachment":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/media?parent=2465"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/categories?post=2465"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/tags?post=2465"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}