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PROCESSED ANTIGEN CHARACTERIZATION BY MASS SPECTROMETRY

通过质谱法进行抗原表征

基本信息

批准号：
7456406
负责人：
DONALD F HUNT
金额：
$ 66.78万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7456406
关键词：
Antigens Autoimmune Diseases Biological Assay Bioterrorism CD8B1 gene Cell Count Cells Chromatography Chronic Lymphocytic Leukemia Class Computer software Detection Development Diagnosis Disease Epitopes Fourier Transform Goals Graft Rejection Histocompatibility Antigens Class II Immune system Individual Insulin-Dependent Diabetes Mellitus Liquid substance Major Histocompatibility Complex Malignant Neoplasms Mass Spectrum Analysis Melanoma Cell Methods Minor Histocompatibility Antigens Molecular Chaperones Monophenol Monooxygenase Multiple Sclerosis Myelin Basic Proteins Nanotechnology Numbers Patients Peptides Performance Phosphorylation Process Protein Sequence Analysis Renal Cell Carcinoma Research Spondylitis Surface System T-Lymphocyte Tissues Virus Diseases antigen processing bone cancer cell disease characteristic glycosylation graft vs host disease instrument instrumentation mRNA Differential Displays malignant breast neoplasm mass spectrometer melanoma peptide I response vaccine development

项目摘要

Identification of disease associated antigens is an often an important step in the development of vaccines or other immune system modulators that are effective against bacterial and viral infections, cancer, autoimmune disorders, transplant rejection and bioterrorism agents. Proposed here is research to continue the development of instrumentation and methods for the sequence analysis of peptide antigens presented to the immune system in association with class I and class II molecules of the major histocompatibility complex. Routine detection and characterization of disease associated antigens present at the attomole level in a mixture of 10,000 self peptides is the goal. In the proposed research, we will implement our recently developed peak parking technology and nano-flow high performance liquid chrornatography to two new instruments, the linear trap mass spectrometer and the tandem linear trap-Fourier transform mass spectrometer. We will also continue to development the differential display software package which makes it possible to compare class I and class II peptides presented by healthy and diseased cells and then to sequence those peptides that are uniquely characteristic of the disease and likely to be recognized as antigens by the immune system. Additional aims of the proposed research include the following: (1) to identify additional class I peptides recognized by pathogenic CD8(+) T-cells in Type I diabetes, (2) to identify additional minor histocompatibility antigens associated with graft-vs-host disease and tissue transplant rejection, (3) to identify phosphorylated class I peptides presented uniquely on the surface of cancer cells, (4) to identify antigenic class I peptides presented from the prenylated breast cancer antigen, C35, (5) to identify peptide antigens restricted by class I HLA molecules on renal cell carcinoma, (6) to identify an HLA A3 restricted and shared antigen presented on melanoma cells, and (7) to evaluate the processing and mechnanism of presentation for both class I and class II epitopes from tyrosinase that are targets of T cell responses in melanoma.

鉴定与疾病相关的抗原往往是研制疫苗或疫苗的一个重要步骤