CD28 / TP44, a surface glycoprotein present on 80% of peripheral T cells in humans, has been shown to be an important costimulatory receptor in immune checkpoint pathway. This CD28/CD80/CD86 immune checkpoint pathway functions with a costimulatory signal transducing through CD28 / TP44 when T cells encounter an APC expressing either of the CD28 / TP44 ligands CD80 / B7-1 or CD86 / B7-2.
Due to costimulation of T cells, CD28 & CD80 (CD86) immune checkpoint pathway can affect multiple aspects of T cell activation. It will lower the concentration of anti-CD3 required to induce a proliferative response in culture. CD28 & CD80 (CD86) immune checkpoint pathway also markedly enhances the production of lymphokines by helper T cells through transcriptional and posttranscriptional regulation of gene expression, and can activate the cytolytic potential of cytotoxic T cells. Inhibition of CD28 & CD80 (CD86) immune checkpoint pathway in vivo can block xenograft rejection and allograft rejection is significantly delayed. In addition, transfection of B7 into a tumor cell line facilitates recognition and prevention of tumor growth.
Lawrence H. Boise et al. CD28 Costimulation Can Promote T Cell Survival by Enhancing the Expression of Bcl-xL. Immunity; 3: 87-98.
Salomon B et al. B7/CD28 Costimulation Is Essential for the Homeostasis of the CD4+CD25+ Immunoregulatory T Cells that Control Autoimmune Diabetes. Immunity. 2000;12(4):431-40.
|Co-inhibitory immune checkpoint pathways||Co-stimulatory immune checkpoint pathways|
|PD1 & PD-L1 immune checkpoint pathway||CD40 & CD40L immune checkpoint pathway|
|CTLA-4 & CD80 (CD86) immune checkpoint pathway||OX40 & OX40L immune checkpoint pathway|
|B7-H3 / CD276 immune checkpoint pathway||HVEM & LIGHT immune checkpoint pathway|
|B7-H4 / B7S1 / B7x immune checkpoint pathway||CD266 & CD155 immune checkpoint pathway|
|HVEM & BTLA immune checkpoint pathway||GITR & GITR Ligand immune checkpoint pathway|
|HVEM & CD160 immune checkpoint pathway||CD27 & CD70 immune checkpoint pathway|
|LAG3 / CD223 / Lymphocyte activation gene 3 immune checkpoint pathway||4-1BB & 4-1BBL immune checkpoint pathway|
|Galectin-9 & TIM-3 immune checkpoint pathway||ICOS & ICOS Ligand immune checkpoint pathway|
|Indoleamine 2,3-dioxygenase/IDO immune checkpoint pathway|
|VISTA / B7-H5 / GI24 immune checkpoint pathway|
|CEACAM1 / CD66a immune checkpoint pathway|
|SIRP alpha & CD47 immune checkpoint pathway|
|2B4 & CD48 immune checkpoint pathway|
|TIGIT & CD155 immune checkpoint pathway|