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Reliable, easy-to-read patient information on common medical conditions β€” written in plain language, free of jargon, and grounded in current evidence. Browse the most frequent diagnoses, understand what they mean for everyday life, and learn which steps and questions help you have a focused conversation with your doctor.

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CD8

Introduction

CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR). Like the TCR, CD8 binds to a major histocompatibility complex (MHC) molecule, but is specific for the class I MHC protein.[2] There are two isoforms of the protein, alpha and beta, each encoded by a different gene. In humans, both genes are located on chromosome 2 in position 2p12.

Tissue distribution

Tissue distribution

The CD8 co-receptor is predominantly expressed on the surface of cytotoxic T cells, but can also be found on natural killer cells, cortical thymocytes, and dendritic cells.The CD8 molecule is a marker for cytotoxic T cell population. It is expressed in T cell lymphoblastic lymphoma and hypo-pigmented mycosis fungoides.[3]

Structure

Structure

To function, CD8 forms a dimer, consisting of a pair of CD8 chains. The most common form of CD8 is composed of a CD8-Ξ± and CD8-Ξ² chain, both members of the immunoglobulin superfamily with an immunoglobulin variable (IgV)-like extracellular domain connected to the membrane by a thin stalk, and an intracellular tail. Less-common homodimers of the CD8-Ξ± chain are also expressed on some cells. The molecular weight of each CD8 chain is about 34 kDa.[4] The structure of the CD8 molecule was determined by Leahy, D.J., Axel, R., and Hendrickson, W.A. by X-ray Diffraction at a 2.6A resolution.[1] The structure was determined to have an immunoglobulin-like beta-sandwich folding and 114 amino acid residues. 2% of the protein is wound into Ξ±-helices and 46% into Ξ²-sheets, with the remaining 52% of the molecules remaining in the loop portions.

File:CD8 receptor.svg
Schematic representation of the heterodimeric CD8 co-receptor
Function

Function

The extracellular IgV-like domain of CD8-Ξ± interacts with the Ξ±3 portion of the Class I MHC molecule.[5] This affinity keeps the T cell receptor of the cytotoxic T cell and the target cell bound closely together during antigen-specific activation. Cytotoxic T cells with CD8 surface protein are called CD8+ T cells. The main recognition site is a flexible loop at the Ξ±3 domain of an MHC molecule. This was discovered by doing mutational analyses. The flexible Ξ±3 domain is located between residues 223 and 229 in the genome.[1] In addition to aiding with cytotoxic T cell antigen interactions the CD8 co-receptor also plays a role in T cell signaling. The cytoplasmic tails of the CD8 co-receptor interact with Lck (lymphocyte-specific protein tyrosine kinase). Once the T cell receptor binds its specific antigen Lck phosphorylates the cytoplasmic CD3 and ΞΆ-chains of the TCR complex which initiates a cascade of phosphorylation eventually leading to activation of transcription factors like NFAT, NF-ΞΊB, and AP-1 which affect the expression of certain genes.[6]

References

References

  1. ↑ 1.0 1.1 1.2 PDB: 1cd8​; Leahy DJ, Axel R, Hendrickson WA (March 1992). “Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 A resolution”. Cell. 68 (6): 1145–62. doi:10.1016/0092-8674(92)90085-Q. PMIDΒ 1547508.
  2. ↑ Gao G, Jakobsen B (2000). “Molecular interactions of coreceptor CD8 and MHC class I: the molecular basis for functional coordination with the T-cell receptor”. Immunol Today. 21 (12): 630–6. doi:10.1016/S0167-5699(00)01750-3. PMIDΒ 11114424.
  3. ↑ Leong AS, Cooper K, Leong FJ (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. p.Β 73. ISBNΒ 1-84110-100-1.
  4. ↑ “anti-Human CD8” (PDF). Bangs Laboratories, Inc. 21 March 2013. Archived (PDF) from the original on 2016-10-13. Retrieved 2016-08-18.
  5. ↑ Devine L, Sun J, Barr M, Kavathas P (1999). “Orientation of the Ig domains of CD8 alpha beta relative to MHC class I”. J Immunol. 162 (2): 846–51. PMIDΒ 9916707.
  6. ↑ “CD8 alpha – Marker for cytotoxic T Lymphocytes”. Archived from the original on 21 September 2015. Retrieved 11 January 2016.
External links
  1. ↑ “CD8 alpha – Marker for cytotoxic T lymphocytes”. Archived from the original on 2015-09-21.