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Chemical Compound Review

Glatiramer     (2S)-2-amino-3-(4- hydroxyphenyl)propanoic...

Synonyms: Copolymer i, Glat copolymer, Tgal copolymer, COP 1, AG-E-92460, ...
 
 
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Disease relevance of Copolymer i

 

Psychiatry related information on Copolymer i

  • Mice immunized with TG4 conjugated to human gamma globulin (HGG) produced antibodies that bound (T,G)-A-L and were TGB5 Id+ [5].
 

High impact information on Copolymer i

 

Biological context of Copolymer i

  • Cell-mediated immunity in response to (T,G)-A-L was studied with a radioisotopic footpad assay [10].
  • This proliferation could be almost completely inhibited by either McAb 103 or by conventional anti-(T,G)-A-L antibodies of C3H.SW origin, indicating the cross reaction between the idiotypes expressed on the T cell line and the (T,G)-A-L-specific antibodies [11].
  • The results obtained indicated that the ability to respond to (T,G)-A-L by production of an antigen-specific T cell helper factor is inherited as an autosomal dominant trait linked to the responder HLA haplotype [12].
  • Phenotype correction of Ir-genic control of immune response to (T,G)-A-L conjugated to synthetic polyelectrolytes [13].
  • Experiments in CBA (H-2k) and C57BL/6 (H-2b) strains of mice have shown (T,G)-A-L covalently bound to synthetic polyelectrolytes possessing immunoadjuvant effect to induce a pronounced antibody and cell-mediated immune response irrespective of murine genotype [13].
 

Anatomical context of Copolymer i

 

Associations of Copolymer i with other chemical compounds

  • When C3H/HeN and CBA/J nonresponder mice are immunized with ABA on (T,G)-A-L (an I-A-restricted carrier in responder mice), the responses to ABA-tyr and ABA coupled to a variety of unrelated carriers are solely I-A restricted as determined by inhibition with anti-IA and anti-I-E sera [15].
  • Bromodeoxyuridine and light treatment of alloreactive T cells generated in vitro was used to demonstrate that DAPCs primed with a synthetic polypeptide antigen (T,G)-A-L can stimulate only HLA class II-compatible T lymphocytes [16].
 

Gene context of Copolymer i

  • In the present report, a linear analogue and a series of cyclic semi-mimetic peptides were designed and synthesized based on the human myelin basic protein (MBP(87-99)) epitope (Val87-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro90) and on Copolymer I (a mixture of random polymers of Ala, Gln, Lys and Tyr used to treat MS) [17].
  • Chimeric antibodies to the synthetic polypeptide (Tyr, Glu)-Ala-Lys ((T,G)-A-L) were used to examine C activation by human IgG1 [18].
  • We analyzed several defined sequence peptides to determine whether any might mimic the side-chain epitope(s) on (T,G)-A-L which induce the dominant Id+, H10/V kappa 1+ primary response [5].
  • Among the TGB5 Id+, GT+ antibodies, which dominate the neonatal response to (T,G)-A-L, two VH gene families were used: J558 (high frequency) and 36-60 (low frequency) [14].
  • Copolymer I (COP I), a nonencephalitogenic polypeptide analogous to myelin basic protein, is currently being tested for possible effectiveness in treating MS [19].
 

Analytical, diagnostic and therapeutic context of Copolymer i

References

  1. Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3. Hong, J., Li, N., Zhang, X., Zheng, B., Zhang, J.Z. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. Failure of copolymer I to inhibit the human T-cell response to myelin basic protein. Burns, J., Littlefield, K. Neurology (1991) [Pubmed]
  3. Human cellular immune response to copolymer I and myelin basic protein. Burns, J., Krasner, L.J., Guerrero, F. Neurology (1986) [Pubmed]
  4. Management of relapsing/remitting multiple sclerosis with copolymer 1 (Copaxone). Johnson, K.P. Mult. Scler. (1996) [Pubmed]
  5. A peptide sequence mimics the epitope on the multideterminant antigen (Tyr,Glu)-Ala-Lys that induces the dominant H10/V kappa 1+ primary antibody response. Giorgetti, C.A., Press, J.L. J. Immunol. (1994) [Pubmed]
  6. Discovering the role of the major histocompatibility complex in the immune response. McDevitt, H.O. Annu. Rev. Immunol. (2000) [Pubmed]
  7. Complementation of immune response genes for (T,G)-A-L. Munro, A.J., Taussig, M. Nature (1977) [Pubmed]
  8. Antiidiotype stimulation of antigen-specific antigen-independent antibody responses in vitro. I. Evidence for stimulation of helper T lymphocyte function. Weissberger, H.Z., Shenk, R.R., Dickler, H.B. J. Exp. Med. (1983) [Pubmed]
  9. The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression. Kappler, J.W., Marrack, P. J. Exp. Med. (1978) [Pubmed]
  10. Genetic control of the murine cell-mediated immune response in vivo. II. H-2 linked responsiveness to the synthetic polypeptide poly(Tyr,Glu)-poly(DL-Ala)--poly(Lys). Davis, S., Shearer, G.M., Mozes, E., Sela, M. J. Immunol. (1975) [Pubmed]
  11. Establishment and biological activity of a proliferative anti-idiotype-activated T cell line. Axelrod, O., Stanislawski, M., Mozes, E. Immunol. Lett. (1985) [Pubmed]
  12. HLA-linked immune responsiveness to (T,G)-A-L: a family study. Suez, D., Katz, D., Brautbar, C., Cohen, T., Weisman, Z., Bentwich, Z., Mozes, E. Hum. Immunol. (1985) [Pubmed]
  13. Phenotype correction of Ir-genic control of immune response to (T,G)-A-L conjugated to synthetic polyelectrolytes. Petrov, R.V., Khaitov, R.M., Norimov, A.S., Nekrasov, A.V., Koryakin, S.A. Immunol. Lett. (1986) [Pubmed]
  14. Neonatal and adult primary B cells use the same germ-line VH and V kappa genes in their (T,G)-A-L-specific repertoire. Borriero, L., Giorgetti, C., Smith, G., Landry, D., Selsing, E., Zhukovsky, E., Press, J.L. J. Immunol. (1990) [Pubmed]
  15. ABA-specific responses are I region restricted by the carriers used for immunization. Roy, S., Gold, D.P., Leskowitz, S. J. Immunol. (1986) [Pubmed]
  16. Antigen-presenting cells in human decidual tissue. Oksenberg, J.R., Mor-Yosef, S., Persitz, E., Schenker, Y., Mozes, E., Brautbar, C. American journal of reproductive immunology and microbiology : AJRIM. (1986) [Pubmed]
  17. Treatment of experimental allergic encephalomyelitis (EAE) induced by guinea pig myelin basic protein epitope 72-85 with a human MBP(87-99) analogue and effects of cyclic peptides. Tselios, T., Daliani, I., Probert, L., Deraos, S., Matsoukas, E., Roy, S., Pires, J., Moore, G., Matsoukas, J. Bioorg. Med. Chem. (2000) [Pubmed]
  18. Alteration in H chain V region affects complement activation by chimeric antibodies. Horgan, C., Brown, K., Pincus, S.H. J. Immunol. (1990) [Pubmed]
  19. Immunogenic potentials of copolymer I in normal human lymphocytes. Brosnan, C.F., Litwak, M., Neighbour, P.A., Lyman, W.D., Carter, T.H., Bornstein, M.B., Bloom, B.R. Neurology (1985) [Pubmed]
  20. Efficient genetically controlled formation of antibody to a synthetic antigen [poly(LTyr, LGlu)-poly(DLAla)- -poly(LLys)] covalently bound to a synthetic adjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine). Mozes, E., Sela, M., Chedid, L. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  21. (T,G)-A-L specific immune response potential and HLA typing of Israeli patients with systemic lupus erythematosus. Shalev, Y., Bentwich, Z., Katz, D., Brautbar, C., Mozes, E. Clin. Exp. Immunol. (1985) [Pubmed]
  22. A defect in the humoral immune response to protein antigens and haptens in immunoglobulin mu heavy-chain transgenic mice. Pincus, S.H., Cole, R., Pisetsky, D.S. Mol. Immunol. (1992) [Pubmed]
  23. Variable regions of antibodies to synthetic polypeptides--III. Antibodies arising in response to administration of anti-idiotope. Pincus, S.H., Carmack, C.E. Mol. Immunol. (1992) [Pubmed]
 
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