Mammalian tyrosinase-related protein-1 is recognized by autoantibodies from vitiliginous Smyth chickens. An avian model for human vitiligo.

The Smyth line (SL) chicken is an animal model for the human acquired depigmentary disorder vitiligo. Affected birds from this line express a postnatal loss of melanocytes in feather and ocular tissues. This vitiligo-like depigmentation is considered to be a disorder with two interacting components: melanocyte dysfunctions and autoimmune reactions. Previously, SL chicks were shown to express high levels of circulating autoantibodies that bind to chicken melanocyte proteins with molecular masses between 65 and 80 kd. Three mammalian melanocyte proteins known to have isoforms in this molecular mass range are tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2. Of these, only tyrosinase is reported to be expressed in chicken melanocytes. The results presented in this study indicate that, of these three candidate proteins, TRP-1 is the primary antigen recognized by the SL autoantibodies. SL autoantibodies recognize a chicken melanocyte protein that is different from that of tyrosinase or the candidate chicken TRP-2. In addition, several types of experiments incriminate TRP-1 as the primary mammalian melanocyte antigen recognized by SL autoantibodies. We further verified that chicken melanocytes expressed messages for TRP-1 by finding positive signals on Northern blots of chicken melanocyte RNA probed with mammalian TRP-1 cDNA fragments. Therefore, we conclude from these results that the SL autoantibodies primarily recognize TRP-1 in mammalian melanocytes and suggest that chicken melanocytes express a homologue of TRP-1 (the human gp75 and the murine brown/b locus protein).