送交者: 桂铭 于 2006-4-07, 01:23:38:
Srinivasan R, Houghton AN, Wolchok JD.
Induction of autoantibodies against tyrosinase-related proteins following DNA
vaccination: unexpected reactivity to a protein paralogue.
Cancer Immun. 2002 Jul 19;2:8.
The melanosomal membrane glycoproteins Tyrp1 and Tyrp2 (tyrosinase related protein-1 and -2) are recognized by antibodies and CD8+ T-cells, respectively, in patients with melanoma (1, 2, 3, 4). As such, these and other components of the melanosome have been investigated as potential antigens for melanoma vaccines. We and others have evaluated recombinant proteins, recombinant poxvirus, peptides and DNA vaccines in an effort to develop the most potent means for inducing antibodies and T-cell responses against these antigens. Using xenogeneic (human) DNA vaccines in a C57BL/6 mouse model system, we have previously shown that mice produce antibodies and T-cells recognizing gene products of both the mouse and human orthologues (*5, 6). Specifically, we have observed immunity against mouse Tyrp1 or Tyrp2 when mice were immunized with human TYRP1 or DCT (DOPAchrome tautomerase, hTyrp2) respectively, (!!!)while no response occurs when plasmids encoding the syngeneic (mouse) antigens are used(!!!). The immune responses following immunization with xenogeneic genes resulted in tumor rejection of syngeneic B16 melanoma and autoimmune coat hypopigmentation.
*5：Weber LW, Bowne WB, Wolchok JD, Srinivasan R, Qin J, Moroi Y, Clynes R, Song
P, Lewis JJ, Houghton AN.
Tumor immunity and autoimmunity induced by immunization with homologous DNA.
J Clin Invest. 1998 Sep 15;102(6):1258-64.
虽然机制还没有完全清楚，但魏观察到的现象，别的研究小组也观察到类似的结果。
看来，机体对抗原的识别机制，远比我们目前所知的复杂。魏于全在这个领域，的确走在前面。