CD28

CD28 is the prototypic T cell co-stimulatory receptor (signal 2) that synergizes with TCR engagement (signal 1) to enable full T cell activation. It is a ~44 kDa disulfide-linked homodimer of the immunoglobulin superfamily, containing an extracellular IgV-type domain with a conserved MYPPPY motif that mediates binding to its ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells. CD28 is expressed on nearly all human CD4+ T cells and a substantial fraction of CD8+ T cells. Upon ligation, the cytoplasmic tail recruits signaling molecules via three key motifs: YMNM (binds PI3K p85 subunit and GRB2), PRRP (recruits ITK leading to PLCgamma1 and SLP-76/GADS engagement), and PYAP (binds Lck and assembles PKC-theta at the synapse). These converge on NF-kB, AP-1, and NFAT transcriptional programs and mTOR-dependent metabolic reprogramming to drive IL-2 production, T cell survival, proliferation, and effector differentiation. The inhibitory receptor CTLA-4 competes for the same B7 ligands with higher affinity, providing a critical negative regulatory checkpoint. Inherited CD28 deficiency causes susceptibility to HPV-related verrucosis (IMD123). CD28 localizes to the immune synapse at the T cell-APC interface, where it accelerates Lck recruitment to TCR microclusters and lowers the TCR activation threshold.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

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