scholarly journals Expansion of natural (NK1+) T cells that express alpha beta T cell receptors in transporters associated with antigen presentation-1 null and thymus leukemia antigen positive mice.

1996 ◽  
Vol 184 (4) ◽  
pp. 1579-1584 ◽  
Author(s):  
S Joyce ◽  
I Negishi ◽  
A Boesteanu ◽  
A D DeSilva ◽  
P Sharma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Receptors ◽  
T Cell Development ◽  
Cell Development ◽  
Cell Receptors ◽  
Alpha Beta ◽  
Class Ib ◽  
Selection Of

Thymic selection of natural killer-1+ natural T cells that express alpha beta T cell receptors requires a conserved beta 2-microglobulin-associated molecule, presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that positive selection of natural T cells occurs independent of transporters associated with antigen presentation-1 (TAP-1) function. Moreover, natural T cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o thymocytes, they could play a role in natural T cell development. Of these class Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice. This expansion, as in TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains expressed by natural T cells, suggesting that TL and CD1d impact similar repertoires. Thus TL, in addition to CD1d, plays a role in natural T cell development.

scholarly journals Small nucleolar RNAs are concomitantly down-regulated during murine gamma delta T-cell development.

2019 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
T Cell Development ◽  
Cell Development ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Cell Receptors ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Gamma delta T-cells are a lymphocyte subset that display gamma delta T-cell receptors rather than the alpha beta T-cell receptors that alpha beta T cells like CD4 helper and CD8 cytotoxic T-cells display, and whose function straddles the intersection of innate and adaptive immune cells (1). To understand the transcriptional behavior of gamma delta T-cells during mammalian development, we performed global differential gene expression of datasets encompassing transcriptome data from embryonic and adult gamma delta T-cells from mice (2). These analyses revealed a species of non-coding RNA termed small nucleolar RNA, or snoRNA were among the most differentially expressed genes when comparing embryonic and adult gamma delta T-cells. Moreover, these snoRNA were uniformly down-regulated over the course of gamma delta T-cell development. These data demonstrate unprecedented developmental repression of snoRNA in lymphocytes and suggest that stage-specific repression of snoRNAs may serve some vital developmental purpose in the function of gamma delta T-cells.

scholarly journals Thymic Epithelial Cell-Derived IL-15 and IL-15 Receptor α Chain Foster Local Environment for Type 1 Innate Like T Cell Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Huishan Tao ◽  
Lei Li ◽  
Nan-Shih Liao ◽  
Kimberly S. Schluns ◽  
Shirley Luckhart ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Development ◽  
Local Environment ◽  
Cell Development ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Central Tolerance ◽  
Selection Of

Expression of tissue-restricted antigens (TRAs) in thymic epithelial cells (TECs) ensures negative selection of highly self-reactive T cells to establish central tolerance. Whether some of these TRAs could exert their canonical biological functions to shape thymic environment to regulate T cell development is unclear. Analyses of publicly available databases have revealed expression of transcripts at various levels of many cytokines and cytokine receptors such as IL-15, IL-15Rα, IL-13, and IL-23a in both human and mouse TECs. Ablation of either IL-15 or IL-15Rα in TECs selectively impairs type 1 innate like T cell, such as iNKT1 and γδT1 cell, development in the thymus, indicating that TECs not only serve as an important source of IL-15 but also trans-present IL-15 to ensure type 1 innate like T cell development. Because type 1 innate like T cells are proinflammatory, our data suggest the possibility that TEC may intrinsically control thymic inflammatory innate like T cells to influence thymic environment.

scholarly journals Selection of T-cell receptors with a recurrent CDR3β peptide-contact motif within the repertoire of alloreactive CD8+ T cells

2011 ◽  
Vol 41 (8) ◽  
pp. 2414-2423 ◽  
Author(s):  
Caroline Scifo ◽  
Laura Mekaelian ◽  
Elisaphane Munyazesa ◽  
Anne-Marie Schmitt-Verhulst ◽  
Annick Guimezanes
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Receptors ◽  
Cell Receptors ◽  
Selection Of

scholarly journals Characterization of the ligand(s) responsible for negative selection of V beta 11- and V beta 12-expressing T cells: effects of a new Mls determinant.

1990 ◽  
Vol 172 (3) ◽  
pp. 807-813 ◽  
Author(s):  
M S Vacchio ◽  
J J Ryan ◽  
R J Hodes
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Negative Selection ◽  
T Cell Development ◽  
Genetic Regulation ◽  
Gene Products ◽  
Histocompatibility Complex ◽  
Selection Of

During T cell development, events occur that result in the generation of a T cell population capable of recognizing foreign antigens in association with self major histocompatibility complex (MHC) gene products. However, selective events also occur during thymic education that result in the deletion of T cells expressing alpha/beta T cell receptors with high affinity for self determinants alone, i.e., potentially self-reactive T cells. Both MHC- and non-MHC-encoded self antigens appear to play critical roles in this negative selection of self-reactive T cells. We recently observed that T cells expressing V beta 5, V beta 11, V beta 12, or V beta 16 products are deleted in most strains of H-2k type, but not in congenic H-2b strains. In contrast, the H-2k strain C58/J deleted V beta 5+ and V beta 16+ T cells, but failed to delete T cells expressing V beta 11 or V beta 12. Based upon this observation, in the present study we have analyzed the genetic regulation of the ligands responsible for deletion of V beta 11- and V beta 12-expressing T cells, and have tested the possibility that these ligands can function as strong alloantigens analogous to the known minor lymphocyte stimulatory (Mls)- and MHC-encoded antigens. Two major findings have resulted from these studies. First, the ligands recognized by V beta 11+ and V beta 12+ T cells were regulated by both MHC- and multiple non-MHC-encoded genes. Correlation between expression of these two V beta s in backcross animals suggested that shared, though not necessarily identical, ligands mediate deletion of V beta 11- and V beta 12-expressing T cells. Second, the ligand for deletion of V beta 11- and V beta 12-expressing T cells functions as a newly defined Mls alloantigen that stimulates primary proliferative responses in T cell populations from mice that express V beta 11+ and V beta 12+ T cells.

scholarly journals Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers

Nature ◽  
2021 ◽  
Author(s):  
Justina X. Caushi ◽  
Jiajia Zhang ◽  
Zhicheng Ji ◽  
Ajay Vaghasia ◽  
Boyang Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
T Cell Receptors ◽  
Tumour Microenvironment ◽  
Lung Cancers ◽  
Cell Receptors ◽  
Interleukin 7

AbstractPD-1 blockade unleashes CD8 T cells1, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens2, and little is known about transcriptional programs of MANA-specific TIL. Here, we identify MANA-specific T cell clones using the MANA functional expansion of specific T cells assay3 in neoadjuvant anti-PD-1-treated non-small cell lung cancers (NSCLC). We use their T cell receptors as a ‘barcode’ to track and analyse their transcriptional programs in the tumour microenvironment using coupled single-cell RNA sequencing and T cell receptor sequencing. We find both MANA- and virus-specific clones in TIL, regardless of response, and MANA-, influenza- and Epstein–Barr virus-specific TIL each have unique transcriptional programs. Despite exposure to cognate antigen, MANA-specific TIL express an incompletely activated cytolytic program. MANA-specific CD8 T cells have hallmark transcriptional programs of tissue-resident memory (TRM) cells, but low levels of interleukin-7 receptor (IL-7R) and are functionally less responsive to interleukin-7 (IL-7) compared with influenza-specific TRM cells. Compared with those from responding tumours, MANA-specific clones from non-responding tumours express T cell receptors with markedly lower ligand-dependent signalling, are largely confined to HOBIThigh TRM subsets, and coordinately upregulate checkpoints, killer inhibitory receptors and inhibitors of T cell activation. These findings provide important insights for overcoming resistance to PD-1 blockade.

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