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Gene Review

Tap1  -  transporter 1, ATP-binding cassette, sub...

Mus musculus

Synonyms: ABC17, APT1, ATP-binding cassette sub-family B member 2, Abcb2, Antigen peptide transporter 1, ...
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Disease relevance of Tap1

  • In this study, we demonstrate that, similar to lymphoma cell lines with mutations in Tap-1 or Tap-2, the reduced expression of class I molecules on the surface of lymphocytes from diabetes-prone female NOD mice was normalized by incubation at low temperatures or by exposure to class I allele-specific peptides [1].
  • Superinfection with VV-mtp1 and VV-mtp2 rendered both cell lines, after infection with either VV-Kk and VV-Kd, susceptible to lysis by either Kk- or Kd-restricted VV-immune Tc cells [2].

High impact information on Tap1

  • These data indicate that both MHC-linked transporter genes are probably required for class I antigen processing, and that the functional transporter in this pathway may consist of a Ham-1/Ham-2 heterodimer [3].
  • Evidence for such a function has come from the rescue of class I surface expression by a cloned copy of the human homologue of Ham-1, PSF-1, in a human cell line that is defective in antigen processing [3].
  • Like the corresponding genes RING4, HAM1 and mtp1, PSF is related to the multidrug-resistance family of transporters and may be a peptide pump, as translocation of peptides across membranes must occur independently of the secretory pathway [4].
  • Introduction of transgenes encoding either NP34 or NP68 along with an endoplasmic reticulum signal sequence enabled Tap-1-independent expression of each peptide in these mice [5].
  • In this study we analyzed the effects of a transgene encoding an antagonist peptide (influenza NP34) that is presented by H-2Db in a Tap-1-independent fashion in mice expressing the influenza NP68-specific TCR F5 [6].

Biological context of Tap1


Anatomical context of Tap1

  • To test whether this effect depended on an intact immune system, we generated heteroplasmic mice missing functional copies of Tap1, beta2m or Rag1 to impair presentation or recognition of mtDNA-encoded peptides [11].
  • Lmp2 and Tap1 are genes located in the MHC class II region, and they encode proteins participating in the generation and transport of endogenous peptides for T cell education [7].
  • In macrophages from STAT-1 knockout mice, neither LPS nor TNF-alpha induced the expression of Tap1 or Lmp2 [12].
  • The Tap-1 and Tap-2 genes presumably encode a heterodimeric protein complex responsible for transporting endogenous immunogenic peptides to the lumen of the endoplasmic reticulum [13].
  • NOD mice possess a rare Tap-1 allele (Tap-1b); this is associated with reduced Tap-1 mRNA abundance in lymphocytes from diabetes-prone females and decreased conformationally correct class I molecules on the cell surface [1].

Regulatory relationships of Tap1


Other interactions of Tap1

  • By making deletions of the promoter, we determined that only the proximal GAS box is required for LPS induction of Tap1 and Lmp2 [12].
  • The shared promoter contains several areas that can be controlled by STAT-1, such as the proximal and distal IFN-gamma activation site (GAS) boxes in the direction of the Tap1 gene [12].
  • Thus, the Tap-1 3' end gene region and the Lmp-7 initial translation codon are separated by an 1182 nucleotide region which contains a TATA-box, a cAMP regulatory element, two SP1 sites, and two G-C-rich regions [15].
  • To distinguish further between epitopes II and III, Y-2 and Y-3 CTL clones were reacted with SV40-transformed cells bearing mutations in the major histocompatibility complex class I antigen [16].

Analytical, diagnostic and therapeutic context of Tap1


  1. Abnormal class I assembly and peptide presentation in the nonobese diabetic mouse. Li, F., Guo, J., Fu, Y., Yan, G., Faustman, D. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Polymorphic peptide transporters in MHC class I monomorphic Syrian hamster. Lobigs, M., Rothenfluh, H.S., Blanden, R.V., Müllbacher, A. Immunogenetics (1995) [Pubmed]
  3. Ham-2 corrects the class I antigen-processing defect in RMA-S cells. Attaya, M., Jameson, S., Martinez, C.K., Hermel, E., Aldrich, C., Forman, J., Lindahl, K.F., Bevan, M.J., Monaco, J.J. Nature (1992) [Pubmed]
  4. Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter. Spies, T., DeMars, R. Nature (1991) [Pubmed]
  5. High- and low-affinity single-peptide/MHC ligands have distinct effects on the development of mucosal CD8alphaalpha and CD8alphabeta T lymphocytes. Levelt, C.N., de Jong, Y.P., Mizoguchi, E., O'Farrelly, C., Bhan, A.K., Tonegawa, S., Terhorst, C., Simpson, S.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  6. Inhibition of intrathymic T cell development by expression of a transgenic antagonist peptide. Levelt, C.N., Mizoguchi, E., Huang, X., Zacks, R., Bhan, A.K., Tonegawa, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Reduced expression of Tap1 and Lmp2 antigen-processing genes in the nonobese diabetic (NOD) mouse due to a mutation in their shared bidirectional promoter. Yan, G., Fu, Y., Faustman, D.L. J. Immunol. (1997) [Pubmed]
  8. Regulation of Ped gene expression by TAP protein. Ke, X., Warner, C.M. J. Reprod. Immunol. (2000) [Pubmed]
  9. Genomic organization of the mouse Lmp-2 gene and characteristic structure of its promoter. Kishi, F., Suminami, Y., Monaco, J.J. Gene (1993) [Pubmed]
  10. Polymorphism in the mouse Tap-1 gene. Association with abnormal CD8+ T cell development in the nonobese nondiabetic mouse. Pearce, R.B., Trigler, L., Svaasand, E.K., Peterson, C.M. J. Immunol. (1993) [Pubmed]
  11. Mitochondrial DNA segregation in hematopoietic lineages does not depend on MHC presentation of mitochondrially encoded peptides. Battersby, B.J., Redpath, M.E., Shoubridge, E.A. Hum. Mol. Genet. (2005) [Pubmed]
  12. STAT1 regulates lipopolysaccharide- and TNF-alpha-dependent expression of transporter associated with antigen processing 1 and low molecular mass polypeptide 2 genes in macrophages by distinct mechanisms. Marqués, L., Brucet, M., Lloberas, J., Celada, A. J. Immunol. (2004) [Pubmed]
  13. Molecular basis of genetic polymorphism in major histocompatibility complex-linked proteasome gene (Lmp-2). Zhou, P., Cao, H., Smart, M., David, C. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  14. Positive selection of self- and alloreactive CD8+ T cells in Tap-1 mutant mice. Aldrich, C.J., Ljunggren, H.G., Van Kaer, L., Ashton-Rickardt, P.G., Tonegawa, S., Forman, J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  15. Genomic organization and tissue expression of the mouse proteasome gene Lmp-7. Zanelli, E., Zhou, P., Cao, H., Smart, M.K., David, C.S. Immunogenetics (1993) [Pubmed]
  16. Dissection of H-2Db-restricted cytotoxic T-lymphocyte epitopes on simian virus 40 T antigen by the use of synthetic peptides and H-2Dbm mutants. Tevethia, S.S., Lewis, M., Tanaka, Y., Milici, J., Knowles, B., Maloy, W.L., Anderson, R. J. Virol. (1990) [Pubmed]
  17. Levels of Tap-1 and Tap-2 mRNA and expression of Kd and Db on splenic lymphocytes are normal in NOD mice. Pearce, R.B., Trigler, L., Svaasand, E.K., Chen, H.M., Peterson, C.M. Diabetes (1995) [Pubmed]
  18. Treatment with 8-MOP and UVA enhances MHC class I synthesis in RMA cells: preliminary results. Moor, A.C., Schmitt, I.M., Beijersbergen van Henegouwen, G.M., Chimenti, S., Edelson, R.L., Gasparro, F.P. J. Photochem. Photobiol. B, Biol. (1995) [Pubmed]
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