Identification of human T cell epitopes in the Mycobacterium leprae heat shock protein 70-kD antigen
| Autor: | Elizabeth Adams, Warwick J. Britton, Antony Basten, A. L. Goodsall, A. Morgan |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
T-Lymphocytes
T cell Molecular Sequence Data Immunology Lymphocyte Activation Peripheral blood mononuclear cell Epitope Microbiology Mycobacterium tuberculosis Epitopes Immune system Antigen Leprosy Heat shock protein medicine Humans Immunology and Allergy Amino Acid Sequence Tuberculosis Pulmonary Mycobacterium leprae Heat-Shock Proteins Antigens Bacterial Sequence Homology Amino Acid biology biology.organism_classification Recombinant Proteins Molecular Weight medicine.anatomical_structure BCG Vaccine Peptides Research Article |
| Zdroj: | Clinical and Experimental Immunology. 94:500-506 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1111/j.1365-2249.1993.tb08225.x |
| Popis: | SUMMARY In a number of pathogens, heat shock proteins (hsp) stimulate humoral and cellular immune responses despite significant sequence identity with host hsp. The 70-kD hsp of Mycobacterium leprae, whieh shares 47% identity with human hsp70 at the protein level, elicited a T cell response in most Myco. bovis (bacille Calmette Guérin (BCG)) vaccinees as well as leprosy and tuberculosis patients and their contacts. In order to locate T cell epitopes, DNA fragments encoding portions of the 70-kD hsp were expressed in the vector pGEX-2T and tested for T cell reactivity in an in vitro proliferative assay. Cultures of peripheral blood mononuclear cells (PBMC) from BCG vaccinees indicated that the C-terminal half of the molecule contained multiple T cell epitopes, as the T cells from a majority of Myco. leprae hsp70-reactive individuals responded to C-344. Lower proportions of patients with paucibacillary leprosy (36%) and tuberculosis patients (16%) responded to C-344. The smaller C-142 fragment which includes the terminal 70 residues unique to Myco. leprae and is the target for the human antibody response elicited a cellular response in few patients and no vaccinees. In order to map T cell epitopes, two series of synthetic peptides encompassing the region 278–502 were prepared. Using overlapping 12mer and 20mer peptides, this region of the molecule was found to contain several potential T cell epitopes. The longer peptides gave a clearer indication of reactive sequences including regions of the molecule which were not identified with the 12mer peptides. Fine mapping of reactive peptide pools using the 12mer peptides identified two T cell epitopes. Although both were located in regions of the molecule shared with Myco. tuberculosis, one appeared to be cross-reactive with the equivalent human sequence, and thus has the potential to initiate autoimmune responses. |
| Databáze: | OpenAIRE |
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