Disease relevance of Tap2

• 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].
• LT-IIa(T14I) and LT-IIa(T14D) had extremely diminished toxicities in a mouse Y1 adrenal cell bioassay and reduced abilities to induce the accumulation of intracellular cyclic AMP in a macrophage cell line [2].
• Here we demonstrate Sendai virus antigen presentation by the HAM2 (murine TAP2, transporter associated with antigen presentation type 2)-defective RMA-S cell line and compare antigen presentation after restoration of the defect by murine TAP1/2 gene transfection [3].

Psychiatry related information on Tap2

• The effect observed in the Y-1 cell line which expresses apoE may implicate a possible role of this protein in the process of neuronal death that occurred in the Alzheimer's disease [4].

High impact information on Tap2

• 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 [5].
• Ham-2 corrects the class I antigen-processing defect in RMA-S cells [5].
• Here we show that expression of a cloned copy of the Ham-2 gene in RMA-S cells results in recovery of the ability to process and present class I-restricted antigens to cytotoxic T lymphocytes, and in partial recovery of class I surface expression [5].
• There are genes (called HAM1 and HAM2 in the mouse) in this region that encode proteins postulated to be involved in the transport of peptide fragments into the endoplasmic reticulum for association with newly synthesized class I molecules [6].
• Two closely related genes in this region, HAM1 and HAM2, were cloned and had sequence similarities to a superfamily of genes involved in the ATP-dependent transport of a variety of substrates across cell membranes [7].

Biological context of Tap2

• In addition to the differential expression of MHC class I pathway genes, two cell lines representing competent (FF) and defective (BHK) antigen presentation phenotypes for mouse class I MHC restriction elements demonstrated substantial sequence polymorphism in Tap1 but not Tap2 [8].
• The murine major histocompatibility complex (MHC) contains two genes (Ham-1 and Ham-2) that encode members of a super-family of ATP-dependent transport proteins [5].
• The tissue distribution of HAM1 transcripts is consistent with its proposed role in class I-restricted antigen processing, whereas HAM2 transcription appears more restricted and may be involved in antigen processing for class II-restricted T cells [9].
• This defect can be overcome by transfection of RMA-S cells with the Tap-2 gene (formerly Ham-2) that encodes an ATP-binding transporter protein [10].
• However, only one copy of the HAM2 gene is present in RMA-S cells, and it contains a point mutation that leads to a premature stop codon [11].

Anatomical context of Tap2

• 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 [12].
• After exposure to the resident-intruder test, expression of c-fos mRNA in Y1-knockout mice is significantly increased in the medial amygdala, consistent with the activation of centers known to be important in regulating aggressive behavior [13].
• Poly(A+) RNA was isolated from Y1 and Kin mutant cells and was translated in a cell-free, reticulocyte lysate system in the presence of L-[35S]methionine [14].
• We first showed that nuclear extracts from bovine adrenal glands interact with the mouse steroidogenic regulatory elements, forming complexes indistinguishable from those produced by nuclear extracts from mouse Y1 adrenocortical cells [15].
• METHODS: Cultured male donor myoblasts were injected into muscles of female host mice and surviving donor male DNA (myoblasts) quantified using a Y-chromosome specific (Y1) probe [16].

Associations of Tap2 with chemical compounds

• Y1 receptors regulate aggressive behavior by modulating serotonin pathways [13].
• The molecular basis for altered cyclic AMP-dependent protein kinase activity was examined in three different mutant clones (Kin-1, Kin-7, and Kin-8) derived from the Y1 mouse adrenocortical cell line [14].
• Y1 cells were arrested in the G1 phase of the cell cycle by serum starvation and monitored for progression through S phase by measuring [3H]thymidine incorporation into DNA and by measuring the number of nuclei labeled with bromodeoxyuridine [17].
• On the other hand the steroid dexamethasone increased the density of Y1 receptors by 35% [18].
• NPY had no effect on basal steroid release from the Y-1 cells [18].

Other interactions of Tap2

• Class I histocompatibility antigen display is defective in the RMA-S mutant cell line due to a mutation in the Tap-2 gene, which encodes a peptide transporter [19].
• Alloreactive anti-Qa-1 T cells can be assigned into three different specificity groups based on a Qa-1 modifying gene, Qdm, as well as Qa-1 epitope expression on Tap-2-deficient RMA-S cells [20].

Analytical, diagnostic and therapeutic context of Tap2

• We examined Tap-1 and Tap-2 mRNA levels in NOD/Smrf mice using a reverse transcriptase-polymerase chain reaction method that detects > or = 25% changes in mRNA [21].
• Gel shift analysis indicated that a 29-bp oligonucleotide comprising the two putative kappa B sites, which we refer to as Y1-kappa B sequence, specifically binds kappa B-related complexes in nuclear extracts from rat brain areas, NG108-15 cells, and the murine T cell clone A.E7 [22].

References