scholarly journals Evidence for Distinct Mechanisms in the Shaping of the CD4 T Cell Repertoire in Histologically Distinct Myasthenia Gravis – Associated Thymomas

2001 ◽  
Vol 8 (3-4) ◽  
pp. 279-290 ◽  
Author(s):  
P. Ströbel ◽  
M. Helmreich ◽  
H. Kalbacher ◽  
H. K. Müller-Hermelink ◽  
A. Marx
Keyword(s):  
T Cell ◽  
Myasthenia Gravis ◽  
Positive Selection ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Tumor Subtype ◽  
Cell Repertoire ◽  
Well Differentiated ◽  
The One ◽  
T Cell Maturation

The major histocompatibility complex (MHC) class II is involved both in thymocyte maturation and peptide presentation and might thus play a key role in the pathogenesis of paraneoplastic myasthenia gravis (MG) in thymomas. To further investigate this issue, we analyzed and scored the expression of epithelial class II expression in 35 thymomas (medullary, MDT; mixed, MXT; cortical and well differentiated thymic carcinoma, CT / WDTC) and correlated it with the histological tumor subtype, prevalence of MG and thymocyte maturation, which was analyzed by flow cytometry and RT-PCR. Our results show that both MHC class II expression and thymocyte maturation are highly dependent on the histological tumor subtype. CT / WDTC retain features of the normal outer thymic cortex, namely substantial MHC class II expression together with normal early thymocyte maturation until late phases of positive selection, but disturbed terminal thymopoiesis. By contrast, MDT and MXT retain features of the normal inner cortex and the medulla with low to absent class II expression and highly abnormal early thymocyte maturation including impaired positive selection, while terminal T cell maturation in MXT appeared undisturbed. There was no correlation between MHC class II expression and MG status for a given tumor subtype. In conclusion, our results provide evidence for a different histogenesis of cortical thymomas and well differentiated carcinomas on the one hand and mixed and medullary thymomas on the other.Decreased expression levels of MHC class II, although of crucial importance for abnormal intratumorous maturation, are not sufficient to explain the emergence of paraneoplastic MG.

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.

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 Human T cells respond to mouse mammary tumor virus-encoded superantigen: V beta restriction and conserved evolutionary features.

1993 ◽  
Vol 177 (6) ◽  
pp. 1735-1743 ◽  
Author(s):  
N Labrecque ◽  
H McGrath ◽  
M Subramanyam ◽  
B T Huber ◽  
R P Sékaly
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Cell Response ◽  
Cell Repertoire ◽  
Mammary Tumor Virus ◽  
Human T Cells ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

Mouse mammary tumor virus (MMTV)-encoded superantigens (SAGs) influence the murine T cell repertoire and stimulate a strong mixed lymphocyte response in vitro. These SAGs are encoded by the open reading frame of the 3' long terminal repeat of MMTV, termed MMTV SAGs. The T cell response to MMTV SAGs is V beta restricted and requires expression of the class II molecules of the major histocompatibility complex (MHC) on the presenting cells. While human T cells respond to bacterial SAGs, it is not known if human T cells or human MHC class II molecules can interact with MMTV SAGs. A fibroblastic cell line expressing the human MHC class II molecule HLA-DR1 and the Mtv-7 sag gene encoding Mls-1 was used to stimulate human T cells. We show here that human T cells efficiently proliferate in response to Mls-1 presented by HLA-DR1. This T cell response was inhibited by mAbs directed against CD4 or MHC class II molecules but not by mAbs specific for CD8 or MHC class I molecules. Moreover, the response to Mls-1 was limited to human T cells expressing a restricted set of T cell receptor V beta chains. Human T cells expressing V beta 12, 13, 14, 15, and 23 were selectively amplified after Mtv-7 sag stimulation. Interestingly, these human V beta s share the highest degree of homology with the mouse V beta s interacting with Mls-1. These results show a strong evolutionary conservation of the structures required for the presentation and the response to retrovirally encoded endogenous SAGs, raising the possibility that similar elements operate in humans to shape the T cell repertoire.

Genomic bias of the helper T cell repertoire toward recognition of MHC class II heterodimers

1996 ◽  
Vol 47 (1-2) ◽  
pp. 107
Author(s):  
Zoltan A. Nagy ◽  
Damir Vidovic' ◽  
Natalie Boulanger ◽  
Jeanmarie Guenot ◽  
Kouichi Ito ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Cell Repertoire ◽  
Helper T Cell ◽  
Cell Repertoire

T-Cell Repertoire Development in MHC Class II Deficient Humans

1993 ◽  
pp. 135-140 ◽  
Author(s):  
Marja van Eggermond ◽  
Marijke Lambert ◽  
Françoise Mascart ◽  
Etienne Dupont ◽  
Peter van den Elsen
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Repertoire Development

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
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