Disease relevance of IGKV2D-28

• Here we report the occurrence of the 323/A3 antigen in a large cohort of primary breast tumors (m = 384) and its interrelationship with several clinically important variables [1].
• The product of the MAGE-A3 gene is an attractive candidate for tumor immunotherapy because it is expressed in the majority of melanomas and in a great proportion of other solid tumors [2].
• Also, increased expression of the A3 receptor caused an enhanced cardioprotective effect by the preconditioning ischemia [3].
• A number of MAGE-A3 antigenic peptides presented by HLA class I molecules have been used in clinical trials, and regressions of melanoma metastasis have been observed [4].
• Replication of encephalomyocarditis virus was inhibited strongly by IFN-gamma in clones A1, A2, A3, B3, and B8 and by IFN-alpha in clone A2 [5].

High impact information on IGKV2D-28

• PF1: an A-T hook-containing DNA binding protein from rice that interacts with a functionally defined d(AT)-rich element in the oat phytochrome A3 gene promoter [6].
• Specific and saturable binding of the adenosine receptor agonist N6-(4-amino-3-[125I]iodobenzyl)adenosine [125I]ABA was measured on the human A3 receptor stably expressed in Chinese hamster ovary cells with a Kd = 10 nM [7].
• The tissue distribution of A3 mRNA is more similar to the widespread profile found in sheep than to the restricted profile found in the rat [7].
• The human A3 adenosine receptor was cloned from a striatal cDNA library using a probe derived from the homologous rat sequence [7].
• Higher levels of CT7 and MAGE-A3/6 proteins also correlated with elevated plasma-cell proliferation [8].

Chemical compound and disease context of IGKV2D-28

• Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor [3].
• Association of the 323/A3 surface glycoprotein with tumor characteristics and behavior in human breast cancer [1].
• During simulated ischemia, cultured myocytes with enhanced expression of the human A3 receptor and showed significantly higher ATP content, fewer cells killed, and less creatine kinase released into the medium than either control or mock-transfected myocytes [3].
• Significant upregulation of A3 receptor message in nonpigmented epithelial cells was induced by both hypoxia and oxidative stress in vitro, together with increased levels of inosine, hypoxanthine, and xanthine in the supernatants [9].
• METHODS: We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR (MS-PCR), as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues [10].

Biological context of IGKV2D-28

• Amino acids 1811-1818 of the A3 domain comprise a binding site for factors IX and IXa [11].
• CEA protein is processed and presented on major histocompatibility complex (MHC) proteins for multiple alleles, including HLA A2, A3, and A24 [12].
• Finally, the 125I-labeled A3 domain peptide (Asn235-Arg266) was found to bind to thrombin-activated platelets in a specific, reversible, and saturable manner [13].
• Fine mapping of the heparin-binding site using prekallikrein analogue amino acid substitutions of the synthetic peptide Thr249-Phe260 and alanine scanning of the recombinant A3 indicated that the amino acids Lys252 and Lys253 are important for heparin binding [14].
• Western blot assays revealed that the up-regulation of the A3 subtype after lymphocyte activation was caused by an increase in an enriched CD4+ cell fraction [15].

Anatomical context of IGKV2D-28

• These studies are relevant for the design of multi-epitope vaccines for treating MAGE-A3-expressing tumors through the simultaneous stimulation of CTL and T helper lymphocytes [2].
• Breast cancer cell lines and primary breast tumors expressed beta-hCG, c-Met, beta 1-->4-N-acetylgalactosaminyl-transferase, and MAGE-A3 mRNA [16].
• We report here the identification of a MAGE-A3 epitope, TQHFVQENYLEY, presented to CD4+ T lymphocytes by HLA-DP4 molecules, which are expressed in approximately 76% of Caucasians [4].
• Higher frequencies of 323/A3 protein were found in tumors larger than 2 cm (P = 0.03), tumors with infiltrated lymph nodes (P = 0.01), and tumors without estrogen receptor (P = 0.006) [1].
• The study provides the first proof for the new concept that an increased expression of the human A3 receptor in the cardiac myocyte can be an important cardioprotective therapeutic approach [3].

Associations of IGKV2D-28 with chemical compounds

• The FXI Apple 3 (A3) domain mediates binding to platelets in the presence of HK and zinc ions (Zn(2+)) or prothrombin and calcium ions [17].
• A peptide from the Apple 3 (A3) domain (Asn235-Arg266) inhibits factor XI binding to platelets in the presence of HK (42 nM), CaCl2 (2 mM), and ZnCl2 (25 microM), with a Ki congruent to 10 nM which is identical to the Kd for factor XI binding to platelets [13].
• Functional polymorphism of human glutathione transferase A3: effects on xenobiotic metabolism and steroid biosynthesis [18].
• This result was further corroborated by showing that the two selective A1 and A3 receptor agonists, N-cyclopentyladenosine (CPA) and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide (IB-MECA) respectively, induced bone marrow cell proliferation in a manner similar to adenosine [19].
• This mutation resulted in the deletion of a highly conserved glycine at codon 91 (DeltaG91) and could be associated with an incorrect folding of betaA1/A3 crystallin [20].

Other interactions of IGKV2D-28

• Reduced lineage specificity was also observed for the alleles of the A1/A3/A11/A36groups [21].

Analytical, diagnostic and therapeutic context of IGKV2D-28

• Molecular cloning and characterization of the human A3 adenosine receptor [7].
• These results show that CT7 and MAGE-A3/6 are promising myeloma-associated antigens for application in vaccine immunotherapy [8].
• Frozen, stored tumor tissues were examined by a Western blot procedure, and the level of 323/A3 protein in individual tumors was calculated in arbitrary units based on the integrated Mr 43,000 signal in tumors compared with an MCF-7 internal standard [1].
• Here we examined the expression of class 3 semaphorins (3A, 3B, 3C, 3D, 3E, and 3F) and their receptors (neuropilins 1 and 2, plexins A1, A2, A3, B2, and D1) in undifferentiated and differentiated mouse podocytes using reverse transcriptase-polymerase chain reaction (RT-PCR) [22].
• In situ hybridization identified A3 receptors in mesenchymal cells and eosinophils within the lamina propria of the airways and the adventitia of blood vessels, but not in mast cells [23].

References