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Discovery and Targeting of HIV-1 Associated Antigens

HIV-1 相关抗原的发现和靶向

基本信息

批准号：
8493984
负责人：
William Hildebrand
金额：
$ 47.92万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-07 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8493984
关键词：
Alleles Antibodies Antigen Presentation Antigenic Variation Antigens Antiviral Agents Autoimmune Process Autoimmunity B-Lymphocytes Binding Bypass Cataloging Catalogs Cell Culture Techniques Cell Death Cell Line Cell surface Cells Complex Data Development Epitopes Flow Cytometry Frequencies Goals HIV HIV-1 HLA Antigens Human Immune Immune Targeting Immune response Immune system Infection Infectious Agent Mass Spectrum Analysis Memory Molecular Cloning Monoclonal Antibodies Nature Pattern Peptide Fragments Peptides Peripheral Blood Mononuclear Cell Proteins Proteome Proteomics Public Health Reporter Reverse Transcriptase Polymerase Chain Reaction Sampling Scanning Staining method Stains Surface T cell response T-Cell Antigen Receptor Specificity T-Cell Receptor T-Lymphocyte Testing Vaccination Viral Viral Physiology Viral Proteins Viremia Virus Virus Diseases cellular targeting coping efficacy testing fitness innovation novel response success transmission process vaccination strategy

项目摘要

DESCRIPTION (provided by applicant): While searching for HIV-1 peptides that distinguish the HLA class I of infected cells, we found that a number of host-derived peptides are unique to HIV-1 infected cells. In aim 1 we propose to discover HLA class I presented host peptides that distinguish HIV-1 infected cells. Using a unique immunoproteomics approach we will catalog targets that HIV-1 cannot antigenically vary. Having discovered host peptide/HLA complexes that distinguish infected cells, we will next pursue the immune targeting of these complexes. A concern in targeting host peptides presented by the HLA of HIV-1 infected cells is autoimmunity; T cell responses (including memory responses) might target host peptides on uninfected cells. In aim 2 we will derive monoclonal antibodies that mimic the T cell receptor's specificity for peptide/HLA complexes (TCR mimics or TCRm antibodies). The goal is to passively administer these TCRm antibodies for the targeting of HIV-1 infected cells. In aim 3 the anti-viral activity of these TCRm antibodies will be tested. In summary, we will apply a proven immunoproteomics approach to identify unrealized HLA presented host peptides that distinguish HIV-1 infected cells. Furthermore, we will target HIV-1 specific host peptides with a new class of antibodies: TCRm. These novel antibodies will be systematically tested for antiviral effects in cell lines, primary human PBMC and against primary HIV-1 isolates. The ultimate goal is to test whether passive administration of TCRm antibodies will impact HIV-1 replication while bypassing the autoimmune consequences of targeting host epitopes.) Public Health Statement: HIV has been able to elude or defeat immune responses that directly target the virus. We hypothesize that the indirect targeting of HIV infected cells can block transmission of the virus. The goal of this study is to first identify changes unique to the infected cell and to then indirectly attack HIV by targeting infected cells with a new class of antibodies. We intend to target factors that the virus requires rather than the virus itself.

描述（由申请人提供）：

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Abacavir induces loading of novel self-peptides into HLA-B*57: 01: an autoimmune model for HLA-associated drug hypersensitivity.

DOI：
10.1097/qad.0b013e328355fe8f
发表时间：
2012-07-17
期刊：
AIDS (London, England)
影响因子：
0
作者：
Norcross MA;Luo S;Lu L;Boyne MT;Gomarteli M;Rennels AD;Woodcock J;Margulies DH;McMurtrey C;Vernon S;Hildebrand WH;Buchli R
通讯作者：
Buchli R

Direct interrogation of viral peptides presented by the class I HLA of HIV-infected T cells.

直接询问 HIV 感染 T 细胞的 I 类 HLA 呈递的病毒肽。

DOI：
10.1128/jvi.01914-14
发表时间：
2014
期刊：
Journal of virology
影响因子：
5.4
作者：
Yaciuk,JaneC;Skaley,Matthew;Bardet,Wilfried;Schafer,Fredda;Mojsilovic,Danijela;Cate,Steven;Stewart,ChristopherJ;McMurtrey,Curtis;Jackson,KennethW;Buchli,Rico;Olvera,Alex;Cedeño,Samandhy;Plana,Montserrat;Mothe,Beatriz;Brander
通讯作者：
Brander

Expanding the targets available to therapeutic antibodies via novel disease-specific markers.