Induction of tolerance by allochimeric class I MHC molecules: evidence of immunoregulatory T cells and limited usage of T cell receptor Vβ genes

2000 ◽  
Vol 191 (4) ◽  
pp. S50
Author(s):  
Rafik Ghobrial ◽  
Anna Mhoyan ◽  
Yuan Zhai ◽  
Xiu-Da Shen ◽  
Danyun Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Immunoregulatory T Cells ◽  
T Cell Receptor Vβ ◽  
Induction Of Tolerance

scholarly journals Class I MHC molecules on hematopoietic cells can support intrathymic positive selection of T cell receptor transgenic T cells

1999 ◽  
Vol 96 (20) ◽  
pp. 11470-11475 ◽  
Author(s):  
J. Zerrahn ◽  
A. Volkmann ◽  
M. C. Coles ◽  
W. Held ◽  
F. A. Lemonnier ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Hematopoietic Cells ◽  
Cell Receptor ◽  
Class I ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Selection Of

scholarly journals Clone-specific T cell receptor antagonists of major histocompatibility complex class I-restricted cytotoxic T cells.

1993 ◽  
Vol 177 (6) ◽  
pp. 1541-1550 ◽  
Author(s):  
S C Jameson ◽  
F R Carbone ◽  
M J Bevan
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Histocompatibility Complex ◽  
T Cell Clone

A previous report showed that the proliferative response of helper T cells to class II major histocompatibility complex (MHC)-restricted antigens can be inhibited by analogues of the antigen, which act as T cell receptor (TCR) antagonists. Here we define and analyze peptide variants that antagonize various functions of class I MHC-restricted cytotoxic T lymphocyte (CTL) clones. Of 64 variants at individual TCR contact sites of the Kb-restricted octamer peptide ovalbumin257-264 (OVAp), a very high proportion (40%) antagonized lysis by three OVAp-specific CTL clones. This effect was highly clone specific, since many antagonists for one T cell clone have differential effects on another. We show that this inhibition of CTL function is not a result of T cell-T cell interaction, precluding veto-like phenomena as a mechanism for antagonism. Moreover, we present evidence for direct interaction between the TCR and antagonist-MHC complexes. In further analysis of the T cell response, we found that serine esterase release and cytokine production are susceptible to TCR antagonism similarly to lysis. Ca2+ flux, an early event in signaling, is also inhibited by antagonists but may be more resistant to the antagonist effect than downstream responses.

scholarly journals Increased frequency of T cell receptor V alpha 12.1 expression on CD8+ T cells: evidence that V alpha participates in shaping the peripheral T cell repertoire.

1991 ◽  
Vol 174 (3) ◽  
pp. 639-648 ◽  
Author(s):  
H DerSimonian ◽  
H Band ◽  
M B Brenner
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gene Product ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cell Receptor ◽  
Class I ◽  
Class I Mhc ◽  
Alpha Gene

The T cell receptor repertoire has a potential for vast diversity. However, this diversity is limited by the fact that the majority of thymocytes die as the repertoire is shaped by positive and negative selection events during development. Such thymic selection affecting TCR V beta gene segment usage has been demonstrated in the mouse. However, similar data has not been forthcoming in man, and little is known about the role of the TCR alpha chain in antigen/major histocompatibility complex (MHC) recognition in any species. Here, we used a monoclonal antibody recognizing the TCR V alpha 12.1 gene product to assess the expression of this gene in the peripheral blood of man. In most individuals tested, the percentage of cells expressing V alpha 12.1 was significantly higher in CD8+ T cells than in CD4+ T cells. That the V alpha gene product itself was responsible for this increased expression in CD8+ T cells was underscored by the lack of substantial skewing of V beta usage in the V alpha 12.1-bearing T cells. Moreover, the skewed expression of V alpha 12.1 was already present at birth, indicating that it was likely to be due to a developmental process rather than the result of exposure to environmental antigens. Based on the established role for CD8 in binding to class I MHC molecules, we suggest that increased expression of V alpha 12.1 on CD8+ T cells points to a role for TCR's using V alpha 12.1 in class I MHC/Ag recognition. These results indicate that V alpha gene usage in the peripheral blood of man is not random, and they support a role for V alpha as a participant in the self-MHC recognition process that shapes the TCR repertoire.

scholarly journals Preferential differentiation of T cell receptor specificities based on the MHC glycoproteins encountered during development. Evidence for positive selection.

1989 ◽  
Vol 169 (5) ◽  
pp. 1619-1630 ◽  
Author(s):  
S Marusić-Galesić ◽  
D L Longo ◽  
A M Kruisbeek
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cytotoxic T Cells ◽  
Cell Receptor ◽  
Class I ◽  
Cell Repertoire ◽  
Class I Mhc ◽  
Receptor Repertoire ◽  
Cell Receptor Repertoire

T cells recognize foreign antigens together with those MHC glycoproteins they have encountered during their development in the thymus. How the repertoire of antigen-specific TCRs is selected has not yet been fully defined. We have investigated the T cell repertoire specificities of CD4-CD8+ cytotoxic T cells developing under conditions where one of the class I MHC-encoded molecules is blocked, while other class I-MHC glycoproteins are still expressed. We show that antigen-specific T cells restricted to the blocked class I fail to develop, while generation of other class I-specific T cell proceeds undisturbed. This highly selective perturbation of the T cell receptor repertoire demonstrates that development of CD4-CD8+ T cells with a certain TCR specificity requires expression of particular alleles of class I MHC. Thus, TCR-MHC interactions provide signals essential to the differentiation of precursor T cells.

Topology of T cell receptor-peptide/class I MHC interaction defined by charge reversal complementation and functional analysis

1997 ◽  
Vol 271 (2) ◽  
pp. 278-293 ◽  
Author(s):  
Hsiu-Ching Chang ◽  
Alex Smolyar ◽  
Rebecca Spoerl ◽  
Torsten Witte ◽  
Yasuko Yao ◽  
...  
Keyword(s):  
Functional Analysis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Class I Mhc ◽  
Charge Reversal

scholarly journals Structure of a T cell receptor bound to a class I MHC-peptide complex

1996 ◽  
Vol 52 (a1) ◽  
pp. C218-C218 ◽  
Author(s):  
D. N. Garboczi ◽  
P. Ghosh ◽  
U. Utz ◽  
W. E. Biddison ◽  
D. C. Wiley
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Class I Mhc ◽  
Peptide Complex

scholarly journals Self–class I MHC molecules support survival of naive CD8 T cells, but depress their functional sensitivity through regulation of CD8 expression levels

2009 ◽  
Vol 206 (10) ◽  
pp. 2253-2269 ◽  
Author(s):  
Kensuke Takada ◽  
Stephen C. Jameson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Survival ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Class I ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
T Cell Survival ◽  
And Function

Previous studies have suggested that naive CD8 T cells require self-peptide–major histocompatability complex (MHC) complexes for maintenance. However, interpretation of such studies is complicated because of the involvement of lymphopenic animals, as lymphopenia drastically alters naive T cell homeostasis and function. In this study, we explored naive CD8 T cell survival and function in nonlymphopenic conditions by using bone marrow chimeric donors and hosts in which class I MHC expression is absent or limited to radiosensitive versus radioresistant cells. We found that long-term survival of naive CD8 T cells (but not CD4 T cells) was impaired in the absence of class I MHC. However, distinct from this effect, class I MHC deprivation also enhanced naive CD8 T cell responsiveness to low-affinity (but not high-affinity) peptide–MHC ligands. We found that this improved sensitivity was a consequence of up-regulated CD8 levels, which was mediated through a transcriptional mechanism. Hence, our data suggest that, in a nonlymphopenic setting, self-class I MHC molecules support CD8 T cell survival, but that these interactions also attenuate naive T cell sensitivity by dynamic tuning of CD8 levels.

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