FL-160 proteins of Trypanosoma cruzi are expressed from a multigene family and contain two distinct epitopes that mimic nervous tissues.
The partial sequence of a gene encoding the COOH terminus of a protein of apparent molecular weight of 160 kD associated with the flagellum of trypomastigotes of Trypanosoma cruzi (FL-160 now renamed to FL-160-1) has been previously reported. The COOH terminus of FL-160-1 has an epitope, defined by 12 amino acids, which molecularly miMics a nervous tissue antigen of 48 kD found in myenteric plexus, sciatic nerve, and a subset of cells in the central nervous system. We now report that FL-160 is a family of highly related genes. The sequence has been determined for the entire open reading frame (ORF) of one of the members of the FL-160 gene family (FL-160-2) and three other partial ORFs. Sequence analysis reveals the various members of the FL-160 gene family to be approximately 80% homologous in the predicted amino acid sequence, but all retain the 12-amino acid molecular mimicry epitope on the COOH terminus. Comparison of the sequence of FL-160-2 to other sequences demonstrates amino acid homology to bacterial sialidase (27%), members of the SA85 gene family (25-30%) and the shed acute-phase antigen/neuraminidase/trans-sialidase gene family (25-30%). Quantitative hybridization at high stringency suggests 750 copies of FL-160 are present in the DNA of each parasite. Reverse transcription and sequence analysis demonstrates that at least five of the members of the FL-160 gene family are transcribed. The NH2 terminus of one of the FL-160 gene products was expressed and antibodies prepared. Antibodies directed to either the COOH or the NH2 terminus of FL-160 bind a 160-kD T. cruzi protein. Both antibodies bind the surface membrane in the flagellar pocket of the trypomastigote. Antibodies to the NH2 terminus bind epineurium and scattered linear densities in sciatic nerve in a pattern distinct from the pattern with antibodies to the COOH terminus. Thus, there are at least two distinct molecular mimicry epitopes on the FL-160 molecule and both mimic epitopes found in nervous tissues. FL-160 may be involved in the generation of autoimmunity to nervous tissues by molecular mimicry, observed in chronic Chagas' disease.
Van Voorhis
W C
WC
Department of Medicine, School of Medicine, University of Washington, Seattle 98195.
Barrett
L
L
Koelling
R
R
Farr
A G
AG
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D003429:Cross Reactions; D016054:DNA, Protozoan; D000939:Epitopes / Q000276:immunology*; D005260:Female; D017125:Genes, Protozoan; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D005810:Multigene Family; D009417:Nerve Tissue / Q000276:immunology*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D011817:Rabbits; D012689:Sequence Homology, Nucleic Acid; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure
D000906:Antibodies; D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D000939:Epitopes; D015800:Protozoan Proteins; C069805:FL-160 antigen, Trypanosoma cruzi