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抗原加工与表位选择的新见解:针对癌症、自身免疫性疾病和传染病的新型免疫治疗策略的开发

New insights in antigen processing and epitope selection: development of novel immunotherapeutic strategies for cancer, autoimmunity and infectious diseases.

作者信息

Haque A, Blum J S

机构信息

Department of Microbiology and Immunology, and Hollings Cancer Center, Medical University of South Carolina, Charleston 29403, USA.

出版信息

J Biol Regul Homeost Agents. 2005 Jul-Dec;19(3-4):93-104.

Abstract

Current evidence suggests that MHC class II-restricted CD4+ T-cells play a crucial role in orchestrating host immune responses against cancer as well as autoimmune and infectious diseases. Antigens must be processed within endosomal and lysosomal compartments of antigen presenting cells (APC) before binding to MHC class II molecules for display to T-cells. Only a limited number of processed peptides termed immunodominant are selected for display by MHC class II molecules and prove capable of inducing strong T-cell responses. Thus processing reactions within APC are of central importance for the development of effective vaccines as they modulate the number of peptide: class II complexes by enhancing or disrupting epitope formation and display. Studies suggest that there are substantial gaps in our knowledge of how antigen processing and presentation by APC regulates epitope selection and immunodominance in disease situations. Here we describe new insights in antigen processing and epitope selection with relevance to immunotherapeutic strategies for cancer, autoimmunity and infectious diseases.

摘要

目前的证据表明,MHC II类分子限制性CD4+ T细胞在协调宿主针对癌症、自身免疫性疾病和感染性疾病的免疫反应中发挥着关键作用。抗原必须在抗原呈递细胞(APC)的内体和溶酶体区室中进行加工,然后才能与MHC II类分子结合,以呈递给T细胞。只有有限数量的经过加工的肽(称为免疫显性肽)被MHC II类分子选择用于呈递,并被证明能够诱导强烈的T细胞反应。因此,APC内的加工反应对于有效疫苗的开发至关重要,因为它们通过增强或破坏表位的形成和呈递来调节肽:II类复合物的数量。研究表明,在疾病情况下,我们对抗抗原呈递细胞加工和呈递抗原如何调节表位选择和免疫显性的了解存在很大差距。在这里,我们描述了与癌症、自身免疫性疾病和感染性疾病的免疫治疗策略相关的抗原加工和表位选择的新见解。

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