scholarly journals Cytotoxic T lymphocyte nonresponsiveness to the male antigen H-Y in the H-2Db mutants bm13 and bm14. Complementation of the response in F1 crosses with the I-Ab mutant bm12 nonresponder and failure of B6 or Db mutant mice tolerant of each other to respond to allogeneic male cells.

1983 ◽  
Vol 158 (5) ◽  
pp. 1537-1546 ◽  
Author(s):  
L P De Waal ◽  
R W Melvold ◽  
C J Melief
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class Ii ◽  
T Helper Cell ◽  
Class I ◽  
F1 Hybrids ◽  
T Helper ◽  
Cell Repertoire ◽  
Ctl Response

The cytotoxic T-lymphocyte (CTL) response against the male-specific antigen H-Y in C57BL/6 (B6, H-2b) mice is regulated by the I-Ab and Db molecules. From previous studies, we concluded that the bm12 I-Ab mutant does not respond to H-Y, because of a deletion in its T-helper-cell repertoire. We now demonstrate that two Db mutants, bm13 and bm14, also fail to generate a CTL response to H-Y. The bm12 class-II mutant on one hand and the bm13 and bm14 class-I mutants on the other complemented each other for the H-Y-specific CTL response in (bm12 X bm13)F1 and (bm 12 X bm 14)F1 hybrids. This indicates that the need for tolerance of the mutant class II and class I molecules in these hybrids does not create deletions in the I-Ab-restricted T helper cell and Db-restricted CTL repertoire for H-Y. This study constitutes the first demonstration with H-2 mutants that a CTL response controlled by class I and class II MHC molecules is complemented in an F1 cross between a class I and a class II nonresponder. (B6 X bm 13)F1 and (B6 X bm 14)F1 hybrids only responded to H-Y when the antigen was presented on F1 or B6 antigen-presenting cells (apc) but not on Db mutant apc. B6 or Db mutant responders rendered neonatally tolerant of each other failed to respond to the H-Y antigen presented on the tolerogenic allogeneic cell. In the tolerized animals, a response was only seen with responder (B6) type T cells and responder type (B6) apc, indicating that both the T cell source and the MHC type of the apc have to be taken into account in this system. Thus, Ir genes may act at the level of both the T cell repertoire and antigen presentation.

scholarly journals T cell receptor genes in a series of class I major histocompatibility complex-restricted cytotoxic T lymphocyte clones specific for a Plasmodium berghei nonapeptide: implications for T cell allelic exclusion and antigen-specific repertoire.

1991 ◽  
Vol 174 (6) ◽  
pp. 1371-1383 ◽  
Author(s):  
J L Casanova ◽  
P Romero ◽  
C Widmann ◽  
P Kourilsky ◽  
J L Maryanski
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Lymphocyte ◽  
Plasmodium Berghei ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Allelic Exclusion ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Histocompatibility Complex

We report here the first extensive study of a T cell repertoire for a class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocyte (CTL) response. We have found that the T cell receptors (TCRs) carried by 28 H-2Kd-restricted CTL clones specific for a single Plasmodium berghei circumsporozoite nonapeptide are highly diverse in terms of V alpha, J alpha, and J beta segments and aminoacid composition of the junctional regions. However, despite this extensive diversity, a high proportion of the TCRs contain the same V beta segment. These results are in contrast to most previously reported T cell responses towards class II MHC-peptide complexes, where the TCR repertoires appeared to be much more limited. In our study, the finding of a dominant V beta in the midst of otherwise highly diverse TCRs suggests the importance of the V beta segment in shaping the T cell repertoire specific for a given MHC-peptide complex. As an additional finding, we observed that nearly all clones have rearranged both TCR alpha loci. Moreover, as many as one-third of the CTL clones that we analyzed apparently display two productive alpha rearrangements. This argues against a regulated model of sequential recombination at the alpha locus and consequently raises the question of whether allelic exclusion of the TCR alpha chain is achieved at all.

scholarly journals In Vivo Induction of a High-Avidity, High-Frequency Cytotoxic T-Lymphocyte Response Is Associated with Antiviral Protective Immunity

2000 ◽  
Vol 74 (13) ◽  
pp. 5769-5775 ◽  
Author(s):  
C. Sedlik ◽  
G. Dadaglio ◽  
M. F. Saron ◽  
E. Deriaud ◽  
M. Rojas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
High Frequency ◽  
Protective Immunity ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
High Avidity ◽  
Ctl Response

ABSTRACT Many approaches are currently being developed to deliver exogenous antigen into the major histocompatibility complex class I-restricted antigen pathway, leading to in vivo priming of CD8+ cytotoxic T cells. One attractive possibility consists of targeting the antigen to phagocytic or macropinocytic antigen-presenting cells. In this study, we demonstrate that strong CD8+ class I-restricted cytotoxic responses are induced upon intraperitoneal immunization of mice with different peptides, characterized as CD8+ T-cell epitopes, bound to 1-μm synthetic latex microspheres and injected in the absence of adjuvant. The cytotoxic response induced against a lymphocytic choriomeningitis virus (LCMV) peptide linked to these microspheres was compared to the cytotoxic T-lymphocyte (CTL) response obtained upon immunization with the nonreplicative porcine parvovirus-like particles (PPV:VLP) carrying the same peptide (PPV:VLP-LCMV) previously described (C. Sedlik, M. F. Saron, J. Sarraseca, I. Casal, and C. Leclerc, Proc. Natl. Acad. Sci. USA 94:7503–7508, 1997). We show that the induction of specific CTL activity by peptides bound to microspheres requires CD4+T-cell help in contrast to the CTL response obtained with the peptide delivered by viral pseudoparticles. Furthermore, PPV:VLP are 100-fold more efficient than microspheres in generating a strong CTL response characterized by a high frequency of specific T cells of high avidity. Moreover, PPV:VLP-LCMV are able to protect mice against a lethal LCMV challenge whereas microspheres carrying the LCMV epitope fail to confer such protection. This study demonstrates the crucial involvement of the frequency and avidity of CTLs in conferring antiviral protective immunity and highlights the importance of considering these parameters when developing new vaccine strategies.

Mls AND THE HELPER T-CELL REPERTOIRE I. Mls as a regulator of T-helper cell activation

1988 ◽  
Vol 15 (1-3) ◽  
pp. 169-174 ◽  
Author(s):  
U. Hämmerling ◽  
M. Toulon ◽  
R. G. E. Palfree ◽  
M. K. Hoffmann
Keyword(s):  
T Cell ◽  
Cell Activation ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Cell Repertoire ◽  
T Helper ◽  
Helper T Cell ◽  
Cell Repertoire

scholarly journals Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the V beta 17 gene segment.

1995 ◽  
Vol 181 (1) ◽  
pp. 79-91 ◽  
Author(s):  
P J Lehner ◽  
E C Wang ◽  
P A Moss ◽  
S Williams ◽  
K Platt ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Influenza A ◽  
Cytotoxic T Lymphocyte ◽  
Gene Segment ◽  
Cell Subpopulation ◽  
Specific Lysis ◽  
Ctl Response ◽  
The Matrix ◽  
Limiting Dilution

The major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) response is important in the clearance of viral infections in humans. After influenza A infection, a peptide from the matrix protein, M58-66, is presented in the context of the MHC allele HLA-A0201 and the resulting CTL response is detectable in most HLA-A0201 subjects. An initial study suggested that M58-66-specific CTL clones show conserved T cell receptor (TCR) alpha and beta gene segments. We have addressed the significance of this observation by determining the expression of V beta 17 during the development of M58-66-specific CTL lines in 21 unrelated HLA-A0201 subjects, and analyzing TCR usage by M58-66-specific CTL clones. TCR V beta 17 was the dominant V beta segment used and CD8 V beta 17 expansion correlated with M58-66-specific lysis. Limiting dilution analysis from five subjects showed the M58-66 CTL precursor frequency to vary between 1/54,000 and less than 1/250,000, and that up to 85% of the matrix peptide (M58-66)-specific CTL used the V beta 17 gene segment. The M58-66 specific CTL response was dependent on previous viral exposure and specific V beta 17 expansion, as it was not found in cord blood, despite a readily expandable V beta 17+ CD8+ T cell subpopulation. Sequence analysis of 38 M58-66-specific V beta 17 transcripts from 13 subjects revealed extensive conservation in the CDR3 region including conservation of an arginine-serine motif. To test the dependence of this CTL response on the V beta 17 gene segment, peripheral blood lymphocytes were depleted of CD8+ TCR V beta 17+ cells, before the generation of M58-66-specific CTL. In most cases such depletion blocked or severely reduced the generation of the M58-66-specific response, and under limiting dilution conditions could abolish M58-66-specific CTL precursors. These studies reveal the dependence of this natural human immune response on a particular TCR gene segment.

Control of Cytotoxic T-Lymphocyte Responses By Class-I and Class-II H-2 Molecules, Studied with H-2 Mutants

Ir Genes ◽  
1983 ◽  
pp. 377-381
Author(s):  
Cornelis J. Melief ◽  
Leo P. de Waal ◽  
Marijke J. Stukart ◽  
W. Martin Kast ◽  
Roger W. Melvold
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class Ii ◽  
Class I ◽  
Lymphocyte Responses

scholarly journals Cytotoxic T-lymphocyte antigen-4 inhibits GATA-3 but not T-bet mRNA expression during T helper cell differentiation

Immunology ◽  
2006 ◽  
Vol 117 (3) ◽  
pp. 358-367 ◽  
Author(s):  
Francesca Nasta ◽  
Vanessa Ubaldi ◽  
Luigia Pace ◽  
Gino Doria ◽  
Claudio Pioli
Keyword(s):  
Cell Differentiation ◽  
Mrna Expression ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Lymphocyte Antigen

Carrier-reactive hapten-specific cytotoxic T lymphocyte clones originate from a highly preselected T cell repertoire: implications for chemical-induced self-reactivity

1995 ◽  
Vol 25 (10) ◽  
pp. 2788-2796 ◽  
Author(s):  
Stefan Martin ◽  
Helga Ruh ◽  
Sabine Hebbelmann ◽  
Ulrike Pflugfelder ◽  
Barbara Rüde ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals Cell-cell interaction in graft rejection responses: induction of anti-allo-class I H-2 tolerance is prevented by immune responses against allo-class II H-2 antigens coexpressed on tolerogen.

1992 ◽  
Vol 175 (1) ◽  
pp. 99-109 ◽  
Author(s):  
S Hori ◽  
S Kitagawa ◽  
H Iwata ◽  
T Ochiai ◽  
K Isono ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Survival ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Cell Interaction ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Class I ◽  
Prolonged Survival ◽  
Spleen Cells

The intravenous sensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bm1 (bm1) spleen cells results in almost complete abrogation of anti-bm1 CD8+ helper (proliferative and interleukin 2-producing) T cell (Th) activities. Although an appreciable portion of CD8+ cytotoxic T lymphocyte (CTL) precursors themselves remained after this regimen, such a residual CTL activity was eliminated after the engrafting of bm1 grafts, and these grafts exhibited prolonged survival. In contrast, the intravenous sensitization with (bm1 x B6-C-H-2bm12 [bm12])F1 cells instead of bm1 cells failed to induce the prolongation of bm1 graft survival as well as bm12 and (bm1 x bm12)F1 graft survival. In the (bm1 x bm12)F1-presensitized B6 mice before as well as after the engrafting of bm1 grafts, anti-bm1 CTL responses that were comparable to or slightly stronger than those observed in unpresensitized mice were induced in the absence of anti-bm1 Th activities. bm1 graft survival was also prolonged by intravenous presensitization with a mixture of bm1 and bm12 cells but not with a mixture of bm1 and (bm1 x bm12)F1 cells. The capacity of CD4+ T cells to reject bm12 grafts was eliminated by intravenous presensitization with antigen-presenting cell (APC)-depleted bm12 spleen cells. However, intravenous presensitization with APC-depleted (bm1 x bm12)F1 cells failed to induce the prolongation of bm1 graft survival under conditions in which appreciably prolonged bm12 graft survival was induced. More surprisingly, bm1 graft survival was not prolonged even when the (bm1 x bm12)F1 cell presensitization was performed in CD4+ T cell-depleted B6 mice. This contrasted with the fact that conventional class I-disparate grafts capable of activating self Ia-restricted CD4+ as well as allo-class I-reactive CD8+ Th exhibited prolonged survival in CD4+ T cell-depleted, class I-disparate cell-presensitized mice. These results indicate that: (a) intravenous presensitization with class I- and II-disparate cells fails to reduce anti-allo-class I rejection responses that would otherwise be eliminated using only class I-disparate cells; (b) such failure is generated according to the coexpression of both classes of alloantigens on a single cell as tolerogen; and (c) allo-class II antigens coexpressed on tolerogen function to activate CD4+ as well as non-CD4+ Th leading to the generation of anti-class I effector T cell responses.

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