Characterization of an antigen shared by human thymic epithelium and human T cell leukemia virus p19 Gag protein.
The molecular basis for cross-reactive antibody binding to human T cell leukemia virus type I (HTLV-I) p19 core protein and human thymic epithelium has been defined with two monoclonal antibodies (mAbs), 12/1-2 and 13B12, raised to HTLV-I p19. The mAb 12/1-2 has previously been shown to react with HTLV-I p19, HTLV-II p22, and antigens of normal human thymic epithelium, placenta, and foreskin, whereas mAb 13B12 binds only to the carboxyl terminus of HTLV-I p19. In the present study, mAb 12/1-2 bound to a subset of Triton X-100-insoluble intermediate filaments in human thymic epithelium also recognized by antikeratin antibodies AE1 and AE3. The mAb 12/1-2 also reacted in Western blot assays with proteins of 54, 46, and 40 kDa present in extracts of human thymic epithelium and with hexameric peptides containing overlapping sequences of HTLV-I p19 with the amino acids IPP (amino acids 117-119). In contrast, the HTLV-I-specific mAb 13B12 did not bind to human thymic epithelium and reacted with a single hexameric peptide containing the carboxy-terminal HTLV-I p19 sequence IPPPYV (amino acids 117-122). Binding of mAb 12/1-2 to thymic epithelium could be inhibited by adsorption with peptide SP-79 containing a C-terminal sequence (amino acids 112-125) of p19. The crossreactive IPP site is within a region of p19 that has been previously shown to be highly immunogenic in HTLV-I-infected individuals and that is also encoded by genes or mRNA of human cytokeratin 17, keratin 4, epidermal cytokeratin 2, and 50-kDa type I epidermal keratin. Thus, our studies define the sequence of a cross-reactive antigen on HTLV-I p19 that is also associated with keratin intermediate filaments from human thymic epithelium and other normal human tissues and that could serve as a focus of an autoimmune response during HTLV-I infection.
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
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Palker
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Vahlne
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002478:Cells, Cultured; D002648:Child; D003001:Cloning, Molecular; D003429:Cross Reactions / Q000276:immunology; D004848:Epithelium / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology*; D015486:HTLV-I Antigens / Q000737:chemistry / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007633:Keratins / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D011863:Radioimmunoassay; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015683:Gene Products, gag; D015486:HTLV-I Antigens; D015682:Retroviridae Proteins, Oncogenic; D054301:gag Gene Products, Human Immunodeficiency Virus; C060955:p19 protein, Human T-lymphotropic virus 1; D007633:Keratins