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Simultaneous cognate epitope recognition by bovine CD4 and CD8 T cells is essential for primary expansion of antigen-specific cytotoxic T-cells following ex vivo stimulation with a candidate Mycobacterium avium subsp. paratuberculosis peptide vaccine
Institution:1. Department of Veterinary Microbiology and Pathology, Washington State University, Pullman WA, USA;2. Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Egypt;3. USDA, ARS, Animal Disease Research Unit, Pullman, WA, USA;4. USDA, ARS, National Animal Disease Center, Ames, IA, USA;5. Veterinary Quarantine of Alexandria, General Organization for Veterinary Services, Ministry of Agriculture and Land Reclamation, Egypt;6. Department of Biotechnology, Inje University, Injero 197, Kimhae-si, Gyeongsangnam-do, Republic of Korea;1. Grupo de Imunologia Celular e Molecular, Fundação Oswaldo Cruz, IRR, Av. Augusto de Lima, 1715 Barro Preto, Belo Horizonte, MG, Brazil;2. Katal Biotecnológica. R. Leiria, 1160 São Francisco, Belo Horizonte, MG 31255-100, Brazil;3. Departamento de Microbiologia, Universidade Federal de Minas Gerais, ICB, Av. Presidente Antônio Carlos, 6627 Pampulha, Belo Horizonte, MG, Brazil;4. Hospital das Clínicas da Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 110 Santa Efigênia, Belo Horizonte, MG 30130-100, Brazil;5. Vaccine Research and Development Center, Department of Physiology, University of California Irvine, USA;1. School of Medicine, Department of Infectious Disease, Nankai University Second People''s Hospital, Nankai University, Tianjin 300192, China;2. Tianjin STD and AIDS Prevention and Treatment Association, Tianjin 300192, China;3. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA;4. Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;5. Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA;1. National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture (USDA), Ames, Iowa, USA;2. Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA;3. TB Immunology and Vaccinology, Department of Bacteriology, Animal and Plant Health Agency, New Haw, Addlestone, Surry UK;1. Department of Clinical Laboratory, Kunshan First People''s Hospital, Affiliated to JiangSu University, Kunshan 215300, China;2. Department of Clinical Laboratory, The Second Xiangya Hospital of Central South University, Changsha 410078, China;3. Department of Pathology, ChongQing Cancer Institute, ChongQing 404100, China;1. Ruminant Diseases and Immunology Research Unit, USDA Agricultural Research Service, National Animal Disease Center, Ames, IA 50010;2. Oak Ridge Institute for Science and Education, Oak Ridge Associated Universities, Oak Ridge, TN 37830;3. Immunobiology Interdepartmental Graduate Program, Iowa State University, Ames 50011;1. Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Egypt;2. Department of Transplant and Infection Immunology, Institutes for Infection Medicine, Saarland University, Homburg, Germany;3. Lionex Diagnostics & Therapeutics, Braunschweig, Germany;4. Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Pullman, WA, USA
Abstract:Studies in cattle show CD8 cytotoxic T cells (CTL), with the ability to kill intracellular bacteria, develop following stimulation of monocyte-depleted peripheral blood mononuclear cells (mdPBMC) with antigen presenting cells (APC, i.e. conventional dendritic cells cDC] and monocyte-derived DC MoDC]) pulsed with MMP, a membrane protein from Mycobacterium avium subsp. paratuberculosis (Map) encoded by MAP2121c. CTL activity was diminished if CD4 T cells were depleted from mdPBMC before antigen (Ag) presentation by APC, suggesting simultaneous cognate recognition of MMP epitopes presented by MHC I and MHC II molecules to CD4 and CD8 T cells is essential for development of CTL activity. To explore this possibility, studies were conducted with mdPBMC cultures in the presence of monoclonal antibodies (mAbs) specific for MHC class I and MHC class II molecules. The CTL response of mdPBMC to MMP-pulsed APC was completely blocked in the presence of mAbs to both MHC I and II molecules and also blocked in the presence of mAbs to either MHC I or MHC II alone. The results demonstrate simultaneous cognate recognition of Ag by CD4 and CD8 T cells is essential for delivery of CD4 T cell help to CD8 T cells to elicit development of CTL.
Keywords:Bovine  Dendritic cells  T cells  Paratuberculosis  Cognate epitope recognition  Cytotoxicity  Vaccination  Propidium monoazide  mdPBMC"}  {"#name":"keyword"  "$":{"id":"k0055"}  "$$":[{"#name":"text"  "_":"monocyte-depleted peripheral blood mononuclear cells  cDC"}  {"#name":"keyword"  "$":{"id":"k0065"}  "$$":[{"#name":"text"  "_":"conventional dendritic cells  MoDC"}  {"#name":"keyword"  "$":{"id":"k0075"}  "$$":[{"#name":"text"  "_":"monocyte-derived DC  MoMΦ"}  {"#name":"keyword"  "$":{"id":"k0085"}  "$$":[{"#name":"text"  "_":"monocyte-derived macrophages  WT"}  {"#name":"keyword"  "$":{"id":"k0105"}  "$$":[{"#name":"text"  "_":"wild type  MMP"}  {"#name":"keyword"  "$":{"id":"k0115"}  "$$":[{"#name":"text"  "_":"35 kDa membrane peptide  PMA"}  {"#name":"keyword"  "$":{"id":"k0125"}  "$$":[{"#name":"text"  "_":"Propidium monoazide  qPCR"}  {"#name":"keyword"  "$":{"id":"k0135"}  "$$":[{"#name":"text"  "_":"quantitative PCR  cycle threshold
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