为了阐明草鱼MHC class I等位基因的结构与多态性,进一步研究其与疾病的关系,从草鱼cDNA文库中克隆了MHC class I基因(Ctid-MHC I);并通过对12个个体Ctid-MHC I的克隆,分析了其等位基因的多态性与三级结构.结果显示Ctid-MHC I等位基因在...为了阐明草鱼MHC class I等位基因的结构与多态性,进一步研究其与疾病的关系,从草鱼cDNA文库中克隆了MHC class I基因(Ctid-MHC I);并通过对12个个体Ctid-MHC I的克隆,分析了其等位基因的多态性与三级结构.结果显示Ctid-MHC I等位基因在α1与α2区域变异幅度大,可分为6类(Ctid-MHC I-UA-UF),9型(A-I);但是其三级结构和抗原多肽结合的关键性氨基酸十分保守.结果阐明了草鱼MHC class I分子在8个区域(A-H)置换率高,存在插入或缺失以及长度变异,使等位基因呈现高度多态性.动物MHC class I分子系统树也提示了我国大陆架上鱼类、两栖类、鸟类、哺乳动物和人的遗传距离与分枝年代.展开更多
Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response.Non-self intracellular proteins are processed into short peptides and...Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response.Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class I molecules assisted by several chaperone proteins to form trimeric complex.MHC class I complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells.The cells presenting non-self peptides are cleared by CD8 positive T cells.In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class I expression must be carefully regulated.Many of the cellular components involved in antigen processing and class I presentation are known and their various functions are now becoming clearer.Cellular & Molecular Immunology.2004;1(1):22-30.展开更多
Cancer cells can evade immune recognition by losing major histocompatibility complex(MHC)class Ⅰ.Hence,MHC class Ⅰ-negative cancers represent the most challenging cancers to treat.Chemotherapeutic drugs not only dir...Cancer cells can evade immune recognition by losing major histocompatibility complex(MHC)class Ⅰ.Hence,MHC class Ⅰ-negative cancers represent the most challenging cancers to treat.Chemotherapeutic drugs not only directly kill tumors but also modulate the tumor immune microenvironment However,it remains unknown whether chemotherapy-treated cancer cells can activate CD8 T cells independent of tumor-derived MHC class Ⅰ and whether such MHC class Ⅰ-independent CD8 T-cell activation can be exploited for cancer immunotherapy.Here,we showed that chemotherapy-treated cancer cells directly activated CD8 T cells in an MHC class Ⅰ-independent manner and that these activated CD8 T cells exhibit virtual memory(VM)phenotypes.Consistently,in vivo chemotherapeutic treatment preferentially increased tumor-infiltrating VM CD8 T cells.Mechanistically,MHC class Ⅰ-independent activation of CD8 T cells requires cell-cell contact and activation of the PI3K pathway.VM CD8 T cells contribute to a superior therapeutic effect on MHC class Ⅰ-deficient tumors.Using humanized mouse models or primary human CD8 T cells,we also demonstrated that chemotherapy-treated human lymphomas activated VM CD8 T cells independent of tumor-derived MHC class Ⅰ.In conclusion,CD8 T cells can be directly activated in an MHC class Ⅰ-independent manner by chemotherapy-treated cancers,and these activated CD8 T cells may be exploited for developing new strategies to treat MHC class Ⅰ-deficient cancers.展开更多
Since the publication of the DRiP(defective ribosomal product) hypothesis in 1996, numerous studies have addressed the contribution of DRiPs to generating viral antigenic peptides for CD8^+T cell immunosurveillance. H...Since the publication of the DRiP(defective ribosomal product) hypothesis in 1996, numerous studies have addressed the contribution of DRiPs to generating viral antigenic peptides for CD8^+T cell immunosurveillance. Here, we review studies characterizing the generation of antigenic peptides from influenza A virus encoded DRiPs, discuss the many remaining mysteries regarding the nature of their co-translational generation, and speculate on where the future might lead.展开更多
文摘为了阐明草鱼MHC class I等位基因的结构与多态性,进一步研究其与疾病的关系,从草鱼cDNA文库中克隆了MHC class I基因(Ctid-MHC I);并通过对12个个体Ctid-MHC I的克隆,分析了其等位基因的多态性与三级结构.结果显示Ctid-MHC I等位基因在α1与α2区域变异幅度大,可分为6类(Ctid-MHC I-UA-UF),9型(A-I);但是其三级结构和抗原多肽结合的关键性氨基酸十分保守.结果阐明了草鱼MHC class I分子在8个区域(A-H)置换率高,存在插入或缺失以及长度变异,使等位基因呈现高度多态性.动物MHC class I分子系统树也提示了我国大陆架上鱼类、两栖类、鸟类、哺乳动物和人的遗传距离与分枝年代.
文摘Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response.Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class I molecules assisted by several chaperone proteins to form trimeric complex.MHC class I complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells.The cells presenting non-self peptides are cleared by CD8 positive T cells.In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class I expression must be carefully regulated.Many of the cellular components involved in antigen processing and class I presentation are known and their various functions are now becoming clearer.Cellular & Molecular Immunology.2004;1(1):22-30.
基金supported by University of Colorado School of Medicine and Cancer Center startup funds to JHW,Cancer League of Colorado grants R21-CA184707,R21-Al110777,R01-CA166325,R21 Al133110,and R01-CA229174 to J.H.W.a fund from American Cancer Society(ACS IRG#16-184-56)to Z.C.X.W.was supported by an AAI Careers in Immunology Fellowship+1 种基金supported by an NIH F31 fellowship(F31DE027854)supported by an NIH T32 fellowship(T32 AI007405).
文摘Cancer cells can evade immune recognition by losing major histocompatibility complex(MHC)class Ⅰ.Hence,MHC class Ⅰ-negative cancers represent the most challenging cancers to treat.Chemotherapeutic drugs not only directly kill tumors but also modulate the tumor immune microenvironment However,it remains unknown whether chemotherapy-treated cancer cells can activate CD8 T cells independent of tumor-derived MHC class Ⅰ and whether such MHC class Ⅰ-independent CD8 T-cell activation can be exploited for cancer immunotherapy.Here,we showed that chemotherapy-treated cancer cells directly activated CD8 T cells in an MHC class Ⅰ-independent manner and that these activated CD8 T cells exhibit virtual memory(VM)phenotypes.Consistently,in vivo chemotherapeutic treatment preferentially increased tumor-infiltrating VM CD8 T cells.Mechanistically,MHC class Ⅰ-independent activation of CD8 T cells requires cell-cell contact and activation of the PI3K pathway.VM CD8 T cells contribute to a superior therapeutic effect on MHC class Ⅰ-deficient tumors.Using humanized mouse models or primary human CD8 T cells,we also demonstrated that chemotherapy-treated human lymphomas activated VM CD8 T cells independent of tumor-derived MHC class Ⅰ.In conclusion,CD8 T cells can be directly activated in an MHC class Ⅰ-independent manner by chemotherapy-treated cancers,and these activated CD8 T cells may be exploited for developing new strategies to treat MHC class Ⅰ-deficient cancers.
基金supported by the Division of Intramural Research, NIAID, NIH
文摘Since the publication of the DRiP(defective ribosomal product) hypothesis in 1996, numerous studies have addressed the contribution of DRiPs to generating viral antigenic peptides for CD8^+T cell immunosurveillance. Here, we review studies characterizing the generation of antigenic peptides from influenza A virus encoded DRiPs, discuss the many remaining mysteries regarding the nature of their co-translational generation, and speculate on where the future might lead.
