A patient-derived cytotoxic T-lymphocyte clone and two peptide-dependent monoclonal antibodies recognize HLA-B27-peptide complexes with low stringency for peptide sequences
| Autor: | Juan Wen, K M Williams, E Hermann, R B Raybourne, Feng Huang, X. K. Cheng, G. Roth, Jens G. Kuipers, Herbert Kellner, Jeffrey C. Wang, D K Yu, B Ackermann, W C Tsai |
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| Rok vydání: | 1996 |
| Předmět: |
musculoskeletal diseases
Cytotoxicity Immunologic medicine.drug_class T-Lymphocytes Immunology Molecular Sequence Data Clone (cell biology) Peptide Monoclonal antibody Transfection Microbiology Epitope Mice Structure-Activity Relationship L Cells Antibody Specificity medicine Cytotoxic T cell Animals Humans Amino Acid Sequence Peptide sequence HLA-B27 Antigen chemistry.chemical_classification biology Base Sequence Antibodies Monoclonal Flow Cytometry Molecular biology Clone Cells CTL Infectious Diseases chemistry Mutation biology.protein Parasitology Antibody Oligopeptides Research Article |
| Zdroj: | Infection and immunity. 64(1) |
| ISSN: | 0019-9567 |
| Popis: | HLA-B27 molecules expressed on the T2 mutant cell line do not have peptides. Such empty HLA-B27 molecules were not recognized by an HLA-B27-restricted cytotoxic T-lymphocyte (CTL) clone (auto-1) derived from synovial fluid. To test for peptide dependency of the clone, B27-T2 cells were incubated with a panel of 48 different peptides. This lack of stringency was compared with that of a peptide-dependent monoclonal antibody, B27.M2. Positive B27.M2 reactivity resulted when the B27-T2 cells were incubated with two peptides: RRKAMFEDI and RRMGPPVGHR, derived from Chlamydia HSP60 and human ribonucleoprotein, respectively. Because of the limited availability of CTL versus monoclonal antibody, the specificity of B27.M2 was studied in greater detail. The importance of the HLA-B27 heavy chain in antibody recognition of class I-peptide complexes was demonstrated by site-directed mutagenesis. The stringency of the peptide residues was tested by making analogs of each of the nine residues in RRKAMFEDI, creating a panel of 180 analogs. Although stringency was highest for the sixth position, as many as six different amino acids provided positive reactivity. These results indicate that immune recognition of HLA-B27-peptide complexes might have rather low stringency for the peptide sequences. In theory, then, pathogen-derived peptides which induce autoimmunity by generating autoreactive CTL might not share much sequence similarity with the responsible self peptides. |
| Databáze: | OpenAIRE |
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