Identification of skin gamma delta T cell antigens

皮肤 γ δ T 细胞抗原的鉴定

• 批准号: 8177647
• 负责人: Wendy L. Havran
• 金额: $ 28.43万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8177647
• 关键词: Adult; Antigen Presentation Pathway; Antigen Receptors; Antigens; Autoantigens; Biochemical; Cell physiology; Cells; Chronic; Detection; Development; Disease; Distress; Epithelial; Epithelial Cells; Fractionation; Future; Growth; Growth Factor; High Pressure Liquid Chromatography; Homeostasis; Inflammatory; Injury; Lead; Ligands; Lymphoid; Lytic; Malignant Neoplasms; Monitor; Mono-S; Mus; Pathway interactions; Peptide/MHC Complex; Peptides; Phase; Physiological; Play; Population; Positioning Attribute; Production; Property; Role; Site; Skin; Specificity; Stress; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Testing; Tissues; Trauma; Wound Healing; assault; base; cell injury; chemokine; combinatorial; fighting; insight; intraepithelial; keratinocyte; killings; migration; pathogen; prototype; repaired; response to injury; tissue tropism; tool; tumor; tumor eradication; ultraviolet irradiation; wound

DESCRIPTION (provided by applicant): gd T cells localize to epithelial sites where they play important roles in tissue homeostasis, wound healing, and protection from malignancy. In the skin, dendritic epidermal T cells (DETC) express a unique, monoclonal gd TCR. DETC monitor neighboring epithelial cells for damage or disease. Following recognition of epithelial distress the DETC respond by the production of growth factors and chemokines that modulate keratinocyte proliferation and migration of inflammatory cells. The antigen(s) that active DETC and drive their function are currently unknown. Since all DETC express an identical TCR we hypothesize that these cells will recognize a single or limited set of related antigens. In contrast to ab T cell recognition of specific pathogen peptides presented by MHC molecules, we propose that DETC will see distress-induced self antigens that are commonly expressed after any type of damage or disease. This would allow the population to be broadly specific for local trauma instead of mono-specific for a particular pathogen. This proposal will test these hypotheses through analysis of the antigen specificity of DETC. We have developed new tools for DETC antigen detection that will be used in studies to identify the DETC antigen(s) along with biochemical strategies for antigen characterization. The skin is an important barrier to the outside world and is constantly under assault by pathogens, trauma, and UV irradiation as well as being a common site for malignancy. Information gained about antigens for DETC may lead to the development of a new paradigm for intraepithelial gd T cell antigen recognition and provide tools for future exploitation of the wound healing and lytic properties of these cells to fight malignancy and accelerate repair of chronic wounds. PUBLIC HEALTH RELEVANCE: Narrative Skin gd T cells play important roles in tissue homeostasis, eradication of tumors and wound healing. Identification of the antigens that activate these cells is necessary in order to exploit these cells to fight skin malignancies and increase the efficiency of repair of chronic, non-healing wounds.

描述（由申请人提供）：gd T细胞定位于上皮部位，在组织稳态、伤口愈合和防止恶性肿瘤中发挥重要作用。在皮肤中，树突状表皮T细胞（DETC）表达独特的单克隆gd TCR。DETC监测邻近上皮细胞的损伤或疾病。在识别上皮窘迫之后，DETC通过产生调节角质形成细胞增殖和炎性细胞迁移的生长因子和趋化因子来响应。激活DETC并驱动其功能的抗原目前尚不清楚。由于所有DETC表达相同的TCR，我们假设这些细胞将识别单一或有限的一组相关抗原。与ab T细胞识别MHC分子呈递的特定病原体肽相反，我们提出DETC将看到任何类型的损伤或疾病后通常表达的痛苦诱导的自身抗原。这将允许群体对局部创伤具有广泛特异性，而不是对特定病原体具有单一特异性。本研究拟通过分析DETC的抗原特异性来验证这些假设。我们已经开发了用于DETC抗原检测的新工具，这些工具将用于沿着用于抗原表征的生化策略来鉴定DETC抗原的研究。皮肤是通往外界的重要屏障，经常受到病原体、创伤和紫外线照射的攻击，也是恶性肿瘤的常见部位。获得的关于DETC抗原的信息可能会导致上皮内gd T细胞抗原识别的新范例的发展，并提供工具， 未来开发这些细胞的伤口愈合和溶解特性以对抗恶性肿瘤和加速慢性伤口的修复。 公共卫生相关性：叙述皮肤gd T细胞在组织稳态、根除肿瘤和伤口愈合中发挥重要作用。为了利用这些细胞来对抗皮肤恶性肿瘤并提高慢性、不愈合伤口的修复效率，有必要鉴定激活这些细胞的抗原。