REGULATION OF IMMUNE RESPONSES BY FC PORTION OF ANTIBODY

抗体 FC 部分对免疫反应的调节

• 批准号: 3169347
• 负责人: EDWARD L. MORGAN
• 金额: $ 9.54万
• 依托单位: SCRIPPS CLINIC AND RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-15 至 1986-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3169347
• 关键词: B lymphocyte; T lymphocyte; cell cell interaction; cell mediated cytotoxicity; cellular immunity; humoral immunity; immune complex; immunoglobulins; immunoregulation; leukocyte activation /transformation

The long-term goal of this research is to investigate the mechanism in human B-\and T-cell activation. Studies employing human peripheral blood, tonsil, and splenic lymphocytes indicate that Fc fragments derived from papain digestion, p'Fc fragments derived from plasmin digestion, aggregated immunoglobulin, and immune complexes are potent polyclonal activators. Studies designed to ascertain the cell-cell interaction requirements have revealed that both monocytes and T cells are required for the generation of polyclonal antibody. The role of the monocyte is to enzymatically cleave the Fc fragments into Fc subfragments which then induce Ig secretion. The role of the T cell is to secrete a B-cell differentiation factor (CDF) which in conjunction with Fc subfragments drive B cells to secrete Ig. The active region of the Fc fragment has been localized to approximately the first 24 residues of the CH3 domain [Eu IgG1 335-258] of the molecule. Based on this sequence a 23 residue peptide (p23) was synthesized and found to be a potent lymphocyte activator. Fc fragments derived from a human IgG1 myeloma protein are capable of augmenting the in vitro anti-SRBC response of human PBL. The addition of Fc to cultures of human PBL along with SRBC resulted in a pronounced enhancement of the primary in vitro anti-SRBC response. Augmentation of the immune response is mediated by Fc and not the result of an artifact due to the addition of extraneous protein to culture because neither intact IgG1 nor Fab fragments possess any adjuvant properties. Over the past year, attempts have been made to establish a more relevant in vitro antigen-specific response model. We are currently investigating whether the in vitro antibody response to influenza by human PBL would be suitable. The choice of influenza as the test antigen is ideal since it represents an anamnestic response. (CS)