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Richard A. Flavell

Bio: Richard A. Flavell is an academic researcher from Yale University. The author has contributed to research in topics: Immune system & T cell. The author has an hindex of 231, co-authored 1328 publications receiving 205119 citations. Previous affiliations of Richard A. Flavell include National Institute for Medical Research & University of Michigan.


Papers
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Journal ArticleDOI
TL;DR: It is reported that Hopx+ pTregs converted by DCs from Hopx− T cells are indispensible to sustain tolerance that prevents autoimmune responses directed at self-Ags during experimental acute encephalomyelitis and thatHopx inhibits intrinsic IL-2 expression in pT Regs after antigenic rechallenge.
Abstract: Dendritic cells (DCs) can induce peripheral immune tolerance that prevents autoimmune responses. Ag presentation by peripheral DCs under steady-state conditions leads to a conversion of some peripheral CD4(+) T cells into regulatory T cells (Tregs) that require homeodomain-only protein (Hopx) to mediate T cell unresponsiveness. However, the roles of these peripheral Tregs (pTregs) in averting autoimmune responses, as well as immunological mechanisms of Hopx, remain unknown. We report that Hopx(+) pTregs converted by DCs from Hopx(-) T cells are indispensible to sustain tolerance that prevents autoimmune responses directed at self-Ags during experimental acute encephalomyelitis. Our studies further reveal that Hopx inhibits intrinsic IL-2 expression in pTregs after antigenic rechallenge. In the absence of Hopx, increased levels of IL-2 lead to death and decreased numbers of pTregs. Therefore, formation of Hopx(+) pTregs represents a crucial pathway of sustained tolerance induced by peripheral DCs, and the maintenance of such pTregs and tolerance requires functions of Hopx to block intrinsic IL-2 production in pTregs.

37 citations

Journal ArticleDOI
TL;DR: The present proposal rectifies the existing inconsistencies in the H-2 nomenclature while preserving as much as possible from the previous proposals.
Abstract: The H-2 nomenclature was last revised in 1974 (Klein et al. 1974; Shreffler et al. 1974). Since then it has gradually gone out of step with the advances in molecular biology of the H-2 complex as well as the rules for genetic nomenclature established by the International Committee for Mouse Genetic Nomenclature (Lyon 1989). Furthermore, multiple symbols are currently in use designating the same H-2 genes or their products. The present proposal rectifies the existing inconsistencies in the H-2 nomenclature while preserving as much as possible from the previous proposals.

37 citations

Journal ArticleDOI
TL;DR: Using bacterial fluorescence-activated cell sorting coupled with 16S rRNA gene sequencing (IgA-SEQ), this paper profiled IgA coating of intestinal microbiota in a large cohort of inflammatory bowel disease (IBD) patients and identified bacteria associated with disease and treatment.

37 citations

Journal ArticleDOI
TL;DR: The data suggest that the immune response to a specific B-cell epitope within flagellin, shared by a human neuroblastoma cell line, may be involved in the pathogenesis of neuroborreliosis.
Abstract: Antibodies in sera of 7 patients with neurologic manifestations of Lyme borreliosis and a monoclonal antibody (mAb H9724) to the flagellin of Borrelia burgdorferi have been shown to bind neural tissue. To identify the antibody binding site common to the B. burgdorferi flagellin and the neural tissue, we made recombinant fusion proteins expressing epitopes of flagellin. Antibodies in patients' sera and mAb H9724 bound within an 18-amino acid epitope (residues 208-225) in the central region of flagellin, whereas two other mAbs bound to epitopes mapping elsewhere in the protein. Antibodies in patients sera and mAb H9724 also bound to a human neuroblastoma cell line. Absorption of patients sera with a peptide, EGVQQEGAQQPA, corresponding to amino acids 213-224 of flagellin, inhibited binding to the neuroblastoma cell line. The data suggest that the immune response to a specific B-cell epitope within flagellin, shared by a human neuroblastoma cell line, may be involved in the pathogenesis of neuroborreliosis.

37 citations

Journal ArticleDOI
TL;DR: It is established that L cells transformed with an expression vector containing the Q10 gene secrete a class I molecule which was identified with an antiserum raised against a peptide predicted by the Q 10 transmembrane exon.
Abstract: The DNA sequence of the Q10 genes appears to be highly conserved amongst strains of mice and has only been found to be transcribed in the liver An examination of the nucleotide sequence of the exon that normally encodes the transmembrane domain of class I molecules suggested that the Q10 gene encodes a secreted protein We have established this by showing that L cells transformed with an expression vector containing the Q10 gene secrete a class I molecule which was identified with an antiserum raised against a peptide predicted by the Q10 transmembrane exon Both the L cell-derived Q10 molecule and a class I protein immunoprecipitated from serum with this anti-peptide antiserum have mol wts of approximately 38 000; the Q10 molecule secreted by L cells is heterogeneous in mol wt This heterogeneity was drastically reduced after endoglycosidase F treatment, suggesting that Q10 molecules secreted into the serum by the liver may be glycosylated differently from those secreted by L cells Endoglycosidase F treatment of both the L cell and serum forms of the soluble molecule yielded two products with mol wts of approximately 32 000 and 35 000; this is consistent with the observation that the predicted Q10 protein sequence has two potential glycosylation sites In contrast to previous published results, the Q10 molecule reacted with rabbit anti-H-2 antisera which is consistent with its greater than 80% homology to the classical transplantation antigens

37 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: A procedure for preparing extracts from nuclei of human tissue culture cells that directs accurate transcription initiation in vitro from class II promoters, including tRNA and Ad 2 VA, is developed.
Abstract: We have developed a procedure for preparing extracts from nuclei of human tissue culture cells that directs accurate transcription initiation in vitro from class II promoters. Conditions of extraction and assay have been optimized for maximum activity using the major late promoter of adenovirus 2. The extract also directs accurate transcription initiation from other adenovirus promoters and cellular promoters. The extract also directs accurate transcription initiation from class III promoters (tRNA and Ad 2 VA).

10,800 citations

Journal ArticleDOI
TL;DR: The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptoses in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptotic proteins.
Abstract: The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.

10,744 citations

Journal ArticleDOI
24 Feb 2006-Cell
TL;DR: New insights into innate immunity are changing the way the way the authors think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.

10,685 citations