scholarly journals Inventories of naive and tolerant mouse CD4 T cell repertoires reveal a hierarchy of deleted and diverted T cell receptors

2019 ◽  
Vol 116 (37) ◽  
pp. 18537-18543 ◽  
Author(s):  
Tobias Hassler ◽  
Emanuel Urmann ◽  
Sebastian Teschner ◽  
Christine Federle ◽  
Thamotharampillai Dileepan ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Receptors ◽  
Cd4 T Cell ◽  
Cell Repertoire ◽  
Apparent Lack ◽  
Central Tolerance ◽  
Cell Receptors ◽  
The Central Nervous System ◽  
Antigen Reactivity

Deletion or Tregcell differentiation are alternative fates of autoreactive MHCII-restricted thymocytes. How these different modes of tolerance determine the size and composition of polyclonal cohorts of autoreactive T cells with shared specificity is poorly understood. We addressed how tolerance to a naturally expressed autoantigen of the central nervous system shapes the CD4 T cell repertoire. Specific cells in the tolerant peripheral repertoire either were Foxp3+or displayed anergy hallmarks and, surprisingly, were at least as frequent as in the nontolerant repertoire. Despite this apparent lack of deletional tolerance, repertoire inventories uncovered that some T cell receptors (TCRs) were lost from the CD4 T cell pool, whereas others mediated Tregcell differentiation. The antigen responsiveness of these TCRs supported an affinity model of central tolerance. Importantly, the contribution of different diverter TCRs to the nascent thymic Tregcell population reflected their antigen reactivity rather than their frequency among precursors. This reveals a multilayered TCR hierarchy in CD4 T cell tolerance that separates deleted and diverted TCRs and assures that the Tregcell compartment is filled with cells of maximal permissive antigen reactivity.

Functional characterization of CD4+ T-cell receptors cross-reactive for SARS-CoV-2 and endemic coronaviruses

immuneACCESS ◽  
2021 ◽  
Author(s):  
AG Dykema ◽  
B Zhang ◽  
BA Woldmeskel ◽  
CC Garliss ◽  
LS Cheung ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Functional Characterization ◽  
Cd4 T Cell ◽  
Cell Receptors

A Reliable and Safe T Cell Repertoire based on Low-affinity T Cell Receptors

2001 ◽  
Vol 209 (4) ◽  
pp. 465-486 ◽  
Author(s):  
H.A. VAN DEN BERG ◽  
D.A. RAND ◽  
N.J. BURROUGHS
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Cell Receptors

scholarly journals The CD4+T cell immunodominantAnaplasma marginalemajor surface protein 2 stimulates γδ T cell clones that express unique T cell receptors

2004 ◽  
Vol 77 (2) ◽  
pp. 199-208 ◽  
Author(s):  
Kevin K. Lahmers ◽  
Junzo Norimine ◽  
Mitchell S. Abrahamsen ◽  
Guy H. Palmer ◽  
Wendy C. Brown
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Surface Protein ◽  
Cd4 T Cell ◽  
Γδ T Cell ◽  
T Cell Clones ◽  
Cell Receptors ◽  
Cell Clones

scholarly journals CD1b tetramers bind αβ T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans

2011 ◽  
Vol 208 (9) ◽  
pp. 1741-1747 ◽  
Author(s):  
Anne G. Kasmar ◽  
Ildiko van Rhijn ◽  
Tan-Yun Cheng ◽  
Marie Turner ◽  
Chetan Seshadri ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Direct Detection ◽  
Ex Vivo ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Cell Receptors ◽  
Cell Staining ◽  
Antigen Presenting

Microbial lipids activate T cells by binding directly to CD1 and T cell receptors (TCRs) or by indirect effects on antigen-presenting cells involving induction of lipid autoantigens, CD1 transcription, or cytokine release. To distinguish among direct and indirect mechanisms, we developed fluorescent human CD1b tetramers and measured T cell staining. CD1b tetramer staining of T cells requires glucose monomycolate (GMM) antigens, is specific for TCR structure, and is blocked by a recombinant clonotypic TCR comprised of TRAV17 and TRBV4-1, proving that CD1b–glycolipid complexes bind the TCR. GMM-loaded tetramers brightly stain a small subpopulation of blood-derived cells from humans infected with Mycobacterium tuberculosis, providing direct detection of a CD1b-reactive T cell repertoire. Polyclonal T cells from patients sorted with tetramers are activated by GMM antigens presented by CD1b. Whereas prior studies emphasized CD8+ and CD4−CD8− CD1b-restricted clones, CD1b tetramer-based studies show that nearly all cells express the CD4 co-receptor. These findings prove a cognate mechanism whereby CD1b–glycolipid complexes bind to TCRs. CD1b tetramers detect a natural CD1b-restricted T cell repertoire ex vivo with unexpected features, opening a new investigative path to study the human CD1 system.

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