Tap

transporter associated with antigen processing; ATP-binding cassette, sub-family B; antigen peptide transporter

TAP stands for the acronym "transporter associated with antigen processing" a heterodimeric transporter protein complex. The antigen peptide transporter consists of two proteins encoded by the TAP1 and TAP2 genes, respectively, located on the short arm of chromosome 6 p21.3. TAP is localized in the membrane of the endoplasmic reticulum (ER), and is found in animals as well as fungi.

TAP catalyzes the import of peptides from the cytosol into the endoplasmic reticulum (ER) during antigen presentation. TAP is a transport protein of the so-called ABC transporter family.

Structurally, the TAP protein forms a heterodimer consisting of a transmembrane domain and a nucleotide-binding domain. In the context of antigen presentation (see below Antigen presenting cell), as soon as an antigen is introduced into the ER by means of TAP, the peptide is incorporated into the peptide-binding pocket of the MHC class I complex (if the peptide fits there structurally). The peptide-loaded TAP-assembles with the newly synthesized MHC molecules and 4 chaperones to form the peptide loading complex (PLC) and can then be further processed.

The ATPase activity of TAP is highly dependent on the presence of a correct substrate. This specificity represents an enormously important barrier that prevents unbridled activation of this enzyme complex.

Mutations in the TAP1 or TAP2 gene can lead to various diseases, including immune dysfunction(naked lymphocyte syndrome).

Large DNA viruses have evolved numerous strategies to disrupt the MHC class I antigen presentation pathway. To date, five virally encoded inhibitors have been reported to directly block TAP function:

ICP47 (herpes simplex virus type-1, HSV-1)

US6 (human cytomegalovirus, HCMV)

BNLF2a (Epstein-Barr virus, EBV)

UL49.5 (varicella-zoster virus) and

CPXV12 (smallpox virus).

ICP47 was originally observed as an early HSV-1 gene product that inhibits antigen presentation to CD8+ T cells and was the first TAP inhibitor described.

1. Abele R et al.(2004) The ABCs of immunology: structure and function of TAP, the transporter associatedwith antigen processing. Physiology (Bethesda) 19:216-224.

2. Berger C et al. (2000) Expression of herpes simplex virus ICP47 and human cytomegalovirus US11 prevents recognition of transgene products by CD8(+) cytotoxic T lymphocytes. Journal of Virology 74: 4465-4473.

3. El Hage F et al.(2013) TAP expression level in tumor cells defines the nature and processing of MHC class I peptides for recognition by tumor-specific cytotoxic T lymphocytes. Ann N Y Acad Sci 1283:75-80.

4. Goldsmith K et al (1998) Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response. The Journal of Experimental Medicine 187: 341-348.

5. Matschulla T et al. (2017) A highly conserved sequence of the viral TAP inhibitor ICP47 is required for freezing of the peptide transport cycle. Sci Rep 7:2933.