scholarly journals Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity

Immunology ◽  
2012 ◽  
Vol 137 (3) ◽  
pp. 226-238 ◽  
Author(s):  
Luise U Weigand ◽  
Xiaoling Liang ◽  
Sabine Schmied ◽  
Sabine Mall ◽  
Richard Klar ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Receptors ◽  
Class Ii ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
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

Quantitative but Not Qualitative Variation in MHC Class II Alters CD4 Interaction and Influences T Cell Repertoire Formation

1997 ◽  
Vol 177 (1) ◽  
pp. 49-61
Author(s):  
Sheryl L. Fuller-Espie ◽  
Geraldine A. Murphy ◽  
Sara J. Brett ◽  
Robert I. Lechler
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Qualitative Variation

scholarly journals Quantitative Analysis of the T Cell Repertoire Selected by a Single Peptide–Major Histocompatibility Complex

1998 ◽  
Vol 187 (11) ◽  
pp. 1871-1883 ◽  
Author(s):  
Laurent Gapin ◽  
Yoshinori Fukui ◽  
Jean Kanellopoulos ◽  
Tetsuro Sano ◽  
Armanda Casrouge ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Class Ii ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Histocompatibility Complex ◽  
Single Peptide

The positive selection of CD4+ T cells requires the expression of major histocompatibility complex (MHC) class II molecules in the thymus, but the role of self-peptides complexed to class II molecules is still a matter of debate. Recently, it was observed that transgenic mice expressing a single peptide–MHC class II complex positively select significant numbers of diverse CD4+ T cells in the thymus. However, the number of selected T cell specificities has not been evaluated so far. Here, we have sequenced 700 junctional complementarity determining regions 3 (CDR3) from T cell receptors (TCRs) carrying Vβ11-Jβ1.1 or Vβ12-Jβ1.1 rearrangements. We found that a single peptide–MHC class II complex positively selects at least 105 different Vβ rearrangements. Our data yield a first evaluation of the size of the T cell repertoire. In addition, they provide evidence that the single Eα52-68–I-Ab complex skews the amino acid frequency in the TCR CDR3 loop of positively selected T cells. A detailed analysis of CDR3 sequences indicates that a fraction of the β chain repertoire bears the imprint of the selecting self-peptide.

Interactions of CD4 with MHC class II molecules, T cell receptors and p56 lck

1993 ◽  
Vol 342 (1299) ◽  
pp. 13-24 ◽  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Receptors ◽  
Protein Tyrosine Kinase ◽  
Cell Receptor ◽  
Class Ii ◽  
Cell Receptors ◽  
Multimeric Complex ◽  
And Function ◽  
Immunoglobulin Supergene Family

CD4 and CD8 are members of the immunoglobulin supergene family of proteins, and function as co-receptors with the T cell receptor (TCR) in binding MHC class II or class I molecules, respectively. Within this multimeric complex, CD4 interacts with three distinct ligands. CD4 interacts through its D1 and D2 domains with MHC class II proteins, through its D3 and D4 domains with T cell receptors, and through its cytoplasmic tail with p56 lck , a src -related, protein tyrosine kinase. Each of these interactions is important in the function of CD4 and will be discussed in turn.

scholarly journals Characterization of a library of twenty HBV-specific MHC class II-restricted T cell receptors

2021 ◽  
Author(s):  
Sophia Schreiber ◽  
Melanie Honz ◽  
Weeda Mamozai ◽  
Peter Kurktschiev ◽  
Matthias Schiemann ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Receptors ◽  
Class Ii ◽  
Cell Receptors

scholarly journals Presentation of a self-peptide for in vivo tolerance induction of CD4+ T cells is governed by a processing factor that maps to the class II region of the major histocompatibility complex locus.

1995 ◽  
Vol 182 (5) ◽  
pp. 1481-1491 ◽  
Author(s):  
E V Fedoseyeva ◽  
R C Tam ◽  
P L Orr ◽  
M R Garovoy ◽  
G Benichou
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Tolerance Induction ◽  
Class Ii ◽  
The Self ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Mhc Class Ii Molecules ◽  
Self Peptides

Self-proteins are regularly processed for presentation to autoreactive T cells in association with both class I and class II major histocompatibility complex (MHC) molecules. The presentation of self-peptides plays a crucial role in the acquisition of T cell repertoire during thymic selection. We previously reported that the self-MHC class I peptide Ld 61-80 was immunogenic in syngeneic B10.A mice (H-2a). We showed that despite its high affinity for self-MHC class II molecules, Ld 61-80 peptide failed to induce elimination of autoreactive CD4+ T cells, presumably due to incomplete processing and presentation in the B10.A's developing thymus (cryptic-self peptide). In this report, we showed that the cryptic phenotype was not an intrinsic property of the self-peptide Ld 61-80 since it was found to be naturally presented and subsequently tolerogenic in BALB/c mice (H-2d) (dominant self-peptide). In addition, the self-peptide Ld 61-80 was found to be immunogenic in different H-2a mice while it was invariably tolerogenic in H-2d mice regardless of their background genes. We observed that Ld 61-80 bound equally well to H-2d and H-2k MHC class II molecules. Also, no correlation was found between the quantity of self-Ld protein and the tolerogenicity of Ld 61-80. Surprisingly, Ld 61-80 was not naturally presented in (H-2d x H-2a) F1 mice, indicating that the H-2a MHC locus contained a gene that impaired the presentation of the self-peptide. Analyses of T cell responses to the self-peptide in several H-2 recombinant mice revealed that the presentation of Ld 61-80 was controlled by genes that mapped to a 170-kb portion of the MHC class II region. This study shows that (a) endogenously processed self-peptides presented by MHC class II molecules are involved in shaping the CD4+ T cell repertoire in the thymus; (b) The selection of self-peptides for presentation by MHC class II molecules to nascent autoreactive T cells is influenced by nonstructural MHC genes that map to a 170-kb portion of the MHC class II region; and (c) the MHC locus of H-2a mice encodes factors that prevent or abrogate the presentation by MHC class II molecules of the self-peptide Ld 61-80. These findings may have important implications for understanding the molecular mechanisms involved in T cell repertoire acquisition and self-tolerance induction.

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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