Recombinant Human T-cell surface glycoprotein CD8 alpha chain (CD8A), partial (Active)

Function

Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). This mechanism enables CTLs to recognize and eliminate infected cells and tumor cells. In NK-cells, the presence of CD8A homodimers at the cell surface provides a survival mechanism allowing conjugation and lysis of multiple target cells. CD8A homodimer molecules also promote the survival and differentiation of activated lymphocytes into memory CD8 T-cells

Subcellular Location

Secreted

Disease Association

Immunodeficiency 116 (IMD116) : An autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

CD8 on thymus-derived T-cells usually consists of a disulfide-linked alpha/CD8A and a beta/CD8B chain. Less frequently, CD8 can be expressed as a CD8A homodimer. A subset of natural killer cells, memory T-cells, intraepithelial lymphocytes, monocytes and dendritic cells expresses CD8A homodimers. Expressed at the cell surface of plasmacytoid dendritic cells upon herpes simplex virus-1 stimulation

Subunit

Forms disulfide-linked heterodimers with CD8B at the cell surface. Also forms homodimers in several cell types including NK-cells or peripheral blood T-lymphocytes. Interacts with the MHC class I HLA-A/B2M dimer. One HLA-A molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop) (PubMed:2784196, PubMed:9177355). Interacts with LCK in a zinc-dependent manner. Interacts with HLA-G; this interaction is direct and might down-regulate T cell receptor signaling

• Littman D.R. et al. The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes. — Cell (1985)
• Parnes J.R. et al. Structure of Leu-2/T8 as deduced from the sequence of a cDNA clone. — Behring Inst. Mitt. (1985)
• Sukhatme V.P. et al. The T cell differentiation antigen Leu-2/T8 is homologous to immunoglobulin and T cell receptor variable regions. — Cell (1985)
• Nakayama K. et al. Structure and expression of the gene encoding CD8 alpha chain (Leu-2/T8). — Immunogenetics (1989)
• Norment A.M. et al. Alternatively spliced mRNA encodes a secreted form of human CD8 alpha. Characterization of the human CD8 alpha gene. — J. Immunol. (1989)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Hillier L.W. et al. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. — Nature (2005)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)