ANTIGEN PROCESSING GENES AND CELL BIOLOGY

抗原加工基因和细胞生物学

• 批准号: 6341610
• 负责人: TOM M COTNER
• 金额: $ 21.53万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6341610
• 关键词: MHC class II antigen; alleles; antigen presentation; antigen presenting cell; clinical research; human subject; immunogenetics; intracellular transport; molecular cloning; mutant; protein isoforms; protein transport; reporter genes; tissue /cell culture; transcription factor

DESCRIPTION (Adapted from the Investigator's abstract): The long term objectives of this project are to use genetic and other approaches to identify new genes and gene products involved in HLA class II restricted antigen processing, and to determine how these gene products function. The specific aims of this application are: to determine by complementation analysis whether three new antigen processing mutants, two of which have been shown not to be DM mutants, are affected for the same or different genes; to clone the genes affected in these new antigen processing mutants and in additional mutants which are affected for new antigen processing genes; to further characterize the defects in the three new antigen processing mutants, by run-on transcription, transient expression of DM-reporter constructs, gel shift assays, DM mRNA stability and, when the affected genes are identified, by DNA and protein sequence analysis for domains and motifs informative regarding function, by expression of the protein products of the affected genes, and by the generation of antibodies to the products of the identified genes; to characterize the defects in the affected genes in other antigen processing mutants which define new genes; and to study some aspects of DM function, including characterization of HLA alleles and isotypes which function independently of DM in antigen presentation, and the mapping of functional regions of interaction of DM and class II molecules using transfection of mutated DM and DR genes into DM and DR mutants. The investigators believe that these studies will lead to the identification of new genes and gene products involved in class II restricted antigen processing and an understanding of their functions. Antigen processing has a central role in host defenses against microbial agents and is of likely importance in diseases of autoimmunity. Thus these basic studies should lead to a better understanding of host defense mechanisms, and of ways to enhance host defenses against microorganisms and to ameliorate autoimmune diseases.

描述（改编自研究者摘要）：长期

项目成果

A gene required for class II-restricted antigen presentation maps to the major histocompatibility complex.

• DOI: 10.1084/jem.174.6.1607
• 发表时间: 1991-12-01
• 期刊: The Journal of experimental medicine
• 作者: Mellins E;Kempin S;Smith L;Monji T;Pious D
• 通讯作者: Pious D

Discoordinate surface expression of IFN-gamma-induced HLA class II proteins in nonprofessional antigen-presenting cells with absence of DM and class II colocalization.

• DOI: 10.4049/jimmunol.160.7.3207
• 发表时间: 1998-04
• 期刊: Journal of immunology
• 影响因子: 4.4
• 作者: K. Muczynski;S. Anderson;D. Pious

Invariant-cognate peptide exchange restores class II dimer stability in HLA-DM mutants.

不变同源肽交换可恢复 HLA-DM 突变体中 II 类二聚体的稳定性。

• 发表时间: 1994
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Monji,T;McCormack,AL;Yates3rd,JR;Pious,D
• 通讯作者: Pious,D

Novel mutants define genes required for the expression of human histocompatibility leukocyte antigen DM: evidence for loci on human chromosome 6p.

新型突变体定义了人类组织相容性白细胞抗原DM所需的基因：对人类6p染色体的基因座的证据。

• DOI: 10.1084/jem.186.9.1469
• 发表时间: 1997-11-03
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Fling, SP;Rak, J;Muczynski, KA;Arp, B;Pious, D
• 通讯作者: Pious, D

Exogenously provided peptides fail to complex with intracellular class II molecules for presentation by antigen-presenting cells.

外源提供的肽无法与细胞内 II 类分子复合以供抗原呈递细胞呈递。

• 发表时间: 1997
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Monji,T;Pious,D
• 通讯作者: Pious,D