ANTIBODY RESPONSE IN HUMANS TO PIG XENOANTIGENS

人类对猪异种抗原的抗体反应

• 批准号: 6170363
• 负责人: DONALD V CRAMER
• 金额: $ 28.6万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6170363
• 关键词: B lymphocyte; animal tissue; antibody; antibody formation; antibody specificity; antigen antibody reaction; antigens; enzyme linked immunosorbent assay; gene expression; human genetic material tag; human tissue; humoral immunity; hybridomas; immunogenetics; immunoglobulin genes; liver transplantation; monoclonal antibody; peptide library; polymerase chain reaction; site directed mutagenesis; tissue engineering; transplant rejection; xenotransplantation

The shortage of human organ donors is a critical limitation in the widespread use of transplantation as a treatment for serious diseases. The use of non-human species, particularly the pig, as organ donors offers a potential solution to this shortage of donor organs. The use of tissues from other species (xenografts) has largely been unsuccessful because of a lack of understanding of the nature of the host's immune response to xenografts and the failure of current immunosuppressive techniques to allow for long-term graft survival. The early phases of the xenograft rejection reaction are dominated by humoral immune responses and the experiments proposed in this application are designed to establish a more complete understanding of this component of the host response. We intend identify the immunoglobulin genes that control the antibody response(s) mounted by patients exposed to pig tissues, isolate and characterize human antibodies that have the functional capacity to mediate rejection of pig xenografts, and identify the specific subsets of B lymphocytes that produce these antibodies. Our previous experimental work in rodents has demonstrated the xenograft response appears to be a unique form of T cell-independent antibody production controlled by a closely-related group of Ig genes. We have proposed that this type of immune response is a common feature of the early xenograft reaction, even for diverse species combinations, and the experiments outlined in this proposal are intended to extend these studies to an examination of the human antibody response to pig xenografts. We believe if a small group of closely-related immunoglobulin genes are responsible for controlling the humoral response of xenografts in patients, this information may provide the basis for the development of new strategies for preventing this reaction.

人体器官捐献者的短缺是人体器官移植的一个关键限制