Characteristics of T Cell Receptors

T 细胞受体的特征

基本信息

批准号：
10408695
负责人：
Philippa C. Marrack
金额：
$ 50.72万
依托单位：
NATIONAL JEWISH HEALTH
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-05-01 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10408695
关键词：
Affect Alleles Alpha Cell Animals Antigens Appearance Autoantigens Autoimmune Autoimmune Diseases Autoimmunity Automobile Driving CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes Cells Characteristics Data Development Disease Emulsions Evaluation Funding Heterozygote Human Individual Infection Insulin-Dependent Diabetes Mellitus Knowledge Ligands Major Histocompatibility Complex Mature T-Lymphocyte Methods Mus Nature Parents Peptides Procedures Regulatory T-Lymphocyte Specificity Sum T cell receptor repertoire sequencing T-Cell Receptor T-Lymphocyte T-cell receptor repertoire TRB@ gene cluster Testing Thymus Gland Time Tissues Ursidae Family alpha-beta T-Cell Receptor autoreactive T cell autoreactivity beta Chain Antigen T Cell Receptor deep sequencing disorder risk experimental study improved prevent protective allele receptor terthienyl

项目摘要

Project Summary It is well known that particular major histocompatibility complex (MHC) alleles promote the appearance of many autoimmune diseases. It is also known that certain MHC alleles protect against such illnesses, even in the presence of the disease-promoting allele. Studies over the last 20 years have suggested many explanations for the inhibitory effects of some MHC alleles, with explanations ranging from the fact that the protective alleles may delete or dilute out the potentially damaging T cells to the notion that the protective alleles induce regulatory T cells which prevent attack on the tissue target of autoimmunity. Any of these explanations suggest that MHC heterozygosity affects the T cell receptor (TCR) repertoire and function of the T cells in the animal. A funded R21 supports studies on the effects of MHC heterozygosity on the TCRs bourne by naïve CD4s. Because large scale methods to sequence and identify the TCRα and TCRβ pairs in individual T cells were not available the mice used expressed a single TCRβ. Comparison of the TCRα sequences on naïve CD4 T cells in mice with different MHC alleles showed that, surprisingly, the TCR repertoire of CD4 cells in healthy MHC heterozygous mice was certainly not as large as that of the sum of the two homozygous parents and, in some cases, was considerably lower. Here we would like to find out how the TCR repertoires of CD8 T cells differ between healthy MHC homozygous and heterozygous animals. Other proposed experiments will study the effects of MHC heterozygosity on TCR repertoires in autoimmune prone animals. In this case the mice will express fully functional TCRα and TCRβ loci. Current methods allow knowledge of the pairs of TCRα and TCRβ on relatively few cells (<4000) compared with the total number of TCRα TCRβ pairs (>million) that are present in normal mice or humans. In the experiments proposed here we will adapt current methods in order to develop procedures that will provide greater yields of such pairs. The results of our experiments will inform knowledge of the consequences, for the T cell receptor repertoire, of MHC heterozygosity versus homozygosity in animals with fully functional TCRα and TCRβ loci. The results of such sequencing experiments, combined with data from experiments with tetramers expressing autoantigen MHC/peptide ligands will suggest ideas about how some MHC alleles are protective against autoimmune diseases. The results will also provide more efficient methods of evaluating TCR repertoires in normal individuals.

项目摘要众所周知，特定的主要组织相容性复合物（MHC）等位基因促进了许多自身免疫性疾病。众所周知，某些MHC等位基因也可以防止此类疾病促进疾病的等位基因的存在。过去20年的研究提出了许多解释对于某些MHC等位基因的抑制作用，解释范围从受保护的等位基因可能会删除或稀释潜在的破坏T细胞，以至于受保护等位基因影响的观念调节性T细胞可防止对自身免疫的组织靶标的攻击。这些解释中的任何一个表明MHC杂合性影响T细胞受体（TCR）曲目和T细胞的功能动物。资助的R21支持对幼稚CD4的MHC杂合性对TCRS Bourne的影响的研究。因为在单个T细胞中测序和鉴定TCRα和TCRβ对的大规模方法不是可用的小鼠表示单个TCRβ。在幼稚的CD4 T细胞上的TCRα序列的比较在具有不同MHC等位基因的小鼠中，令人惊讶的是，健康MHC中CD4细胞的TCR曲目杂合小鼠当然不如两个纯合父母的总和，在某些父母的总和中案件较低。在这里，我们想找出CD8 T细胞的TCR曲目如何不同在健康的MHC纯合子和杂合动物之间。其他提出的实验将研究MHC杂合性对自身免疫性TCR库的影响容易发生动物。在这种情况下，小鼠将表达功能性的TCRα和TCRβ基因座。当前方法允许在相对较少的细胞上了解TCRα和TCRβ对的知识（<4000），而总数正常小鼠或人类中存在的TCRαTCRβ对（>百万）。在这里提出的实验中，我们将适应当前方法，以开发将提供此类对收益率更高的过程。我们的实验结果将使T细胞受体库的后果了解具有功能性TCRα和TCRβ基因座的动物中的MHC杂合性与纯合性。结果这种测序实验与表达自身抗原的四聚体的实验的数据结合 MHC/肽配体将提出有关如何保护某些MHC等位基因免受自身免疫性的想法疾病。结果还将提供更有效的方法来评估正常的TCR库个人。

项目成果

期刊论文数量（43）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The T cell receptor: the alpha and beta chains define idiotype, and antigen and MHC specificity.

T 细胞受体：α 和 β 链定义独特型、抗原和 MHC 特异性。

DOI：
10.1016/s0092-8674(85)80103-3
发表时间：
1985
期刊：
Cell
影响因子：
64.5
作者：
Yagüe,J;White,J;Coleclough,C;Kappler,J;Palmer,E;Marrack,P
通讯作者：
Marrack,P

An IL 2-secreting T cell hybridoma that responds to a self class I histocompatibility antigen in the H-2D region.

一种分泌 IL 2 的 T 细胞杂交瘤，可对 H-2D 区域的自身 I 类组织相容性抗原做出反应。

DOI：
发表时间：
1983
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Endres,RO;Marrack,P;Kappler,JW
通讯作者：
Kappler,JW

Vaccine-elicited B and T cell immunity to SARS-CoV-2 is impaired in chronic lung disease patients.

慢性肺病患者中疫苗引发的 B 细胞和 T 细胞对 SARS-CoV-2 的免疫力受损。

DOI：
10.1101/2023.01.25.23284971
发表时间：
2023
期刊：
medRxiv : the preprint server for health sciences
影响因子：
0
作者：
Liu,Haolin;Aviszus,Katja;Zelarney,Pearlanne;Liao,Shu-Yi;Gerber,AnthonyN;Make,Barry;Wechsler,MichaelE;Marrack,Philippa;Reinhardt,RLee
通讯作者：
Reinhardt,RLee

Binding of antigen-specific, H-2-restricted T cell hybridomas to antigen-pulsed adherent cell monolayers.

抗原特异性、H-2 限制性 T 细胞杂交瘤与抗原脉冲的贴壁细胞单层的结合。