Disease relevance of Zfp185

• Interestingly, despite the fact that an overwhelming majority of T cells in the T cell receptor for antigen (TCR)-transgenic mice are specific for P1A, these mice are no more resistant to a P1A-expressing plasmocytoma than nontransgenic littermates [1].
• We report here that the addition of an endoplasmic reticulum-insertion signal sequence at the NH2-terminus of TCD8+ epitopes from chicken ovalbumin (amino acids 257-264) or a naturally occurring tumor antigen expressed by the murine mastocytoma P815 (P1A amino acids 35-43) significantly enhanced the priming of specific TCD8+ in vivo [2].
• The combination of a demethylating agent and adoptive transfer of P1A-specific CTL effectively treated lung metastases in syngeneic mice challenged with P1A-negative 4T1 mammary carcinoma cells [3].
• A similar toxicity was observed after massive expansion of specific CD8+ T cells following immunization with another P815 peptide, which is encoded by gene P1A and was injected in a form covalently linked to an immunostimulatory peptide derived from IL-1 [4].
• P1A viral vector was unable to raise an anti-P815A response in mice that had been previously infected with a recombinant adenovirus carrying the beta-galactosidase gene or with a defective adenovirus [5].

High impact information on Zfp185

• Mature tumor capturing DCs stimulated the differentiation of P1A tumor antigen-specific, CD8+ T cells and uniquely transferred tumor resistance to naive mice [6].
• The immune protection correlates with an enhanced cytotoxic T lymphocyte (CTL) response against P1A, the major tumor antigen expressed in the J558 tumor [7].
• By inference, P1A-specific T cells must have escaped clonal deletion due to low expression of P1A in the thymus [1].
• We report here that although P1A is expressed at low levels in normal tissues, including lymphoid tissues, the P1A-specific transgenic T cells develop normally and remain highly responsive to the P1A antigen [1].
• The V(beta)1- J(beta)1.2 rearrangement is borne by CTL directed against an antigen derived from P1A, a nonmutated mouse self protein which is expressed in P815 but not in normal mouse tissues except testis [8].

Biological context of Zfp185

• Here we used transgenic T cells specific for a natural tumor antigen P1A to evaluate the kinetics, location, and modes of antigen presentation for initiating CTL response in vivo [9].
• Moreover, using genetic models that allow only one mode of antigen presentation, we show here that both cross-presentation of P1A by the host antigen-presenting cells, and direct antigen presentation and costimulation by the tumor cells are sufficient to initiate rapid T cell-clonal expansion in the lymphoid organ [9].
• The induction of P1A expression correlated strongly with demethylation of the CpG island in the promoter region of this gene [3].
• An i.m. DNA-based immunization procedure, consisting of three inoculations with the P1A-coding pBKCMV-P1A plasmid at 10-day intervals, resulted in CTL generation in all treated BALB/c mice [10].
• The gene encoding the Ag P815A, designated P1A, is identical to that encoded in the normal genome of the DBA/2 mouse [11].

Anatomical context of Zfp185

• In situ hybridizations revealed a nonubiquitous and stage-specific expression of Zfp185, especially in differentiating connective tissue [12].
• In this study, we use a transgenic approach to study the development and effector function of T cells specific for P1A, a prototypical unmutated tumor antigen [1].
• Cells from liver, spleen, and a number of mast cell lines were negative, but mast cell line L138.8A produced a high level of P1A message and was lysed by CTL directed against antigens P815A and B. We conclude that major tumor rejection antigens of P815 are encoded by a gene showing little or no expression in most normal cells of adult mice [13].
• Surprisingly, gene gun skin bombardment with the pBKCMV-P1A vector did not induce CTL, nor was it protective against a lethal challenge with the syngeneic P1A-positive J558 tumor cell line [10].
• Transient transfections of constructs containing P1 (3.5 kb) or P2 (2.5 kb) resulted in high levels of reporter gene expression in the RT4-D6P2T schwannoma cell line [14].

Associations of Zfp185 with chemical compounds

• The murine CTA P1A, normally expressed only in a few tumor lines, could be induced de novo in all P1A-negative cancer lines of eight histologic origins in vitro and in various murine xenografts by systemic administration of 5-aza-2'-deoxycytidine [3].
• In order to determine the individual role played by each amino acid residue of P1A 35-43 in binding to H-2Ld and in recognition by anti-A and anti-B T cell receptors (TcR), a series of P1A35-43 peptides substituted by alanine at single positions was synthesized and tested for binding to H-2Ld and for CTL recognition [15].
• Although they interact only with reduced glycoprotein IIIa, these antibodies can be used to design simple tests for the typing of the P1A status of patients [16].

Analytical, diagnostic and therapeutic context of Zfp185

• The weakly immunogenic murine P1A Ag is a useful experimental model for the development of new vaccination strategies that could potentially be used against human tumors [10].
• These results demonstrate that the immune response to P1A is the major component of the tumor rejection response observed in normal mice, and support the use of tumor-specific shared antigens as targets for the immunotherapy of human cancer [17].
• Other Wa- and ST3-derived NMAbs reacted with some or all serotype P1A and P2 HRV strains by neutralization assay and ELISA [18].
• Subcellular fractionation by differential and isopycnic centrifugation indicated that the P1A protein is associated with cytoplasmic membranes demonstrating a broad distribution with respect to size and density [19].
• Immunofluorescence microscopy also revealed a cytoplasmic signal, particularly intense in small vesicles, which coincides with that produced by an anti-mouse type I collagen guinea pig antiserum except near the cell periphery where the P1A signal is weaker [19].

References