泛研网

公众版 查看说明
全球科研项目数据库2026版

Characterization of Lamprey B cells and Antibodies

项目来源

美国卫生和人类服务部基金(HHS)

项目主持人

SINGLETON, KENTNER L

项目受资助机构

EMORY UNIVERSITY

项目编号

5R01AI072435-13

立项年度

2019

立项时间

未公开

项目级别

国家级

研究期限

未知 / 未知

受资助金额

444712.00美元

学科

Biodefense; Biotechnology; Cancer; Emerging Infectious Diseases; Genetics; Infectious Diseases; Rare Diseases; Stem Cell Research; Stem Cell Research - Nonembryonic - Non-Human;

学科代码

未公开

基金类别

Non-SBIR/STTR RPGs

关键词

未公开

参与者

COOPER, MAX DALE

参与机构

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

项目标书摘要：PROJECT SUMMARY As one of two extant jawless vertebrates, lampreys occupy a pivotal position for study of the evolution of our adaptive immune system. The proposed studies build on previous findings indicating that interactive B- and T-like lymphocytes are fundamental features of the adaptive immune system in both jawless and jawed vertebrates, although jawless vertebrates generate variable lymphocyte receptors (VLR) for antigen recognition by combinatorial conversion of incomplete VLRA, VLRB and VLRC germ-line genes into fully assembled VLR genes using neighboring leucine-rich repeat (LRR) sequences as templates. Prior studies indicate that whereas VLRA & VLRC gene assemblies coincide with expression of cytidine deaminase 1 (CDA1) in the thymus equivalent gill region, concurrent VLRB and CDA2 expression occurs primarily in hematopoietic tissues. A comprehensive analysis is proposed to elucidate the development, distribution and function of the VLRB B- like cells and their antibody products in lampreys. The first specific aim is to elucidate the generation, diversification and expression of the VLRB antibody repertoire, with special emphasis on the role of newly identified CDA2 isoforms. The second specific aim is to define the composition and functional capabilities of three key receptors of lamprey B-like lymphocytes, namely the composite VLRB receptor, IL-17D receptor and BAFF/APRIL receptors, through the use of complementary and novel strategies to amplify the assessable VLRB lymphocyte population. The third specific aim is to generate specific VLRB antibodies against human tumor cell antigens and to modify them for diagnostic and potential therapeutic uses. The overall goals of these studies are to better understand basic aspects of B cell biology in a jawless vertebrate, in particular the mechanism of generating VLRB antibody diversity, and to exploit the advantages of lamprey antibodies for biomedical purposes.

  • 排序方式：
  • 1
  • /

  • 1.Evolution of Alternative Adaptive Immune Systems in Vertebrates

    • 关键词：
    • VARIABLE LYMPHOCYTE RECEPTORS; LAMPREY PETROMYZON-MARINUS; DELTA T-CELLS; CHIMERIC ANTIGEN RECEPTORS; CYTIDINE DEAMINASE AID; SEA LAMPREY; SOMATIC DIVERSIFICATION; MONOCLONAL-ANTIBODIES; JAWLESS VERTEBRATES; IMMUNOLOGICAL RESPONSES
    • Boehm, Thomas;Hirano, Masayuki;Holland, Stephen J.;Das, Sabyasachi;Schorpp, Michael;Cooper, Max D.
    • 《ANNUAL REVIEW OF IMMUNOLOGY, VOL 36》
    • 2018年
    • 会议

    Adaptive immunity in jawless fishes is based on antigen recognition by three types of variable lymphocyte receptors (VLRs) composed of variable leucine-rich repeats, which are differentially expressed by two T-like lymphocyte lineages and one B-like lymphocyte lineage. The T-like cells express either VLRAs or VLRCs of yet undefined antigen specificity, whereas the VLRB antibodies secreted by B-like cells bind proteinaceous and carbohydrate antigens. The incomplete VLR germline genes are assembled into functional units by a gene conversion-like mechanism that employs flanking variable leucine-rich repeat sequences as templates in association with lineage-specific expression of cytidine deaminases. B-like cells develop in the hematopoietic typhlosole and kidneys, whereas T-like cells develop in the thymoid, a thymus-equivalent region at the gill fold tips. Thus, the dichotomy between T-like and B-like cells and the presence of dedicated lymphopoietic tissues emerge as ancestral vertebrate features, whereas the somatic diversification of structurally distinct antigen receptor genes evolved independently in jawless and jawed vertebrates.

    ...
  • 排序方式：
  • 1
  • /