scholarly journals Induction of a CD8+ Cytotoxic T Lymphocyte Response by Cross-priming Requires Cognate CD4+ T Cell Help

1997 ◽  
Vol 186 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Sally R.M. Bennett ◽  
Francis R. Carbone ◽  
Freda Karamalis ◽  
Jacques F.A.P. Miller ◽  
William R. Heath
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cd4 T Cell ◽  
Class I ◽  
Cross Tolerance ◽  
Cross Presentation ◽  
Active Involvement ◽  
Transplantation Antigens ◽  
Ctl Induction

Class I–restricted presentation is usually associated with cytoplasmic degradation of cellular proteins and is often considered inaccessible to exogenous antigens. Nonetheless, certain exogenous elements can gain entry into this so-called endogenous pathway by a mechanism termed cross-presentation. This is known to be effective for class I–restricted cytotoxic T lymphocyte (CTL) cross-priming directed against a variety of exogenous tumor, viral, and minor transplantation antigens. The related effect of cross-tolerance can also effectively eliminate responses to selected self components. In both cases, this presentation appears to require the active involvement of a bone marrow–derived antigen presenting cell (APC). Here, we show that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4+ helper T cells. Importantly, this CD4+ population is only effective when both the helper and CTL determinants are recognized on the same APC. Moreover, we would argue that the cognitive nature of this event suggests that the CD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.

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 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.

scholarly journals CD4+ T cell-released exosomes inhibit CD8+ cytotoxic T-lymphocyte responses and antitumor immunity

2010 ◽  
Vol 8 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Haifeng Zhang ◽  
Yufeng Xie ◽  
Wei Li ◽  
Rajni Chibbar ◽  
Sidong Xiong ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Antitumor Immunity ◽  
Cytotoxic T Lymphocyte ◽  
Cd4 T Cell ◽  
Lymphocyte Responses

scholarly journals Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) Can Regulate Dendritic Cell–induced Activation and Cytotoxicity of CD8+ T Cells Independently of CD4+T Cell Help

1999 ◽  
Vol 189 (7) ◽  
pp. 1157-1162 ◽  
Author(s):  
Kathy D. McCoy ◽  
Ian F. Hermans ◽  
J. Henry Fraser ◽  
Graham Le Gros ◽  
Franca Ronchese
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cd8 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Cd4 T Cell ◽  
Cd4 T Cell Help ◽  
T Cell Help

The mechanisms that regulate the strength and duration of CD8+ cytotoxic T cell activity determine the effectiveness of an antitumor immune response. To better understand the antitumor effects of anti-cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) antibody treatment, we analyzed the effect of CTLA-4 signaling on CD8+ T cells in vitro and in vivo. In vitro, cross-linking of CTLA-4 on purified CD8+ T cells caused decreased proliferative responses to anti-CD3 stimulation and rapid loss of activation marker expression. In vivo, blockade of CTLA-4 by neutralizing anti–CTLA-4 mAb greatly enhanced the accumulation, activation, and cytotoxic activity of CD8+ T cells induced by immunization with Ag on dendritic cells (DC). This enhanced response did not require the expression of MHC class II molecules on DC or the presence of CD4+ T cells. These results demonstrate that CTLA-4 blockade is able to directly enhance the proliferation and activation of specific CD8+ T cells, indicating its potential for tumor immunotherapy even in situations in which CD4+ T cell help is limited or absent.

scholarly journals Expression and T cell recognition of hybrid antigens with amino-terminal domains encoded by Qa-2 region of major histocompatibility complex and carboxyl termini of transplantation antigens.

1985 ◽  
Vol 161 (5) ◽  
pp. 935-952 ◽  
Author(s):  
I Stroynowski ◽  
J Forman ◽  
R S Goodenow ◽  
S G Schiffer ◽  
M McMillan ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Coding Region ◽  
Amino Terminal ◽  
L Cells ◽  
Hybrid Class ◽  
Beta 2 Microglobulin ◽  
Transplantation Antigens ◽  
I Gene

Coding potential of the Q6 gene from the Qa-2a region of BALB/c Crgl mice was analyzed by a combination of hybrid class I gene construction and DNA-mediated gene transfer. Recombinant genes were created by exon shuffling of the 5' coding region of the Q6 gene and the 3' coding region of a gene encoding a transplantation antigen (Kd, Dd, or Ld), or the inverse. Some of these hybrid class I genes were expressed in the transfected mouse fibroblasts (L cells). The hybrid class I molecules encoded by the 5' end of the Q6 gene and the 3' end of the Ld gene precipitated as 45,000 mol wt molecules associated with beta 2-microglobulin. The expression of the hybrid proteins indicates that 926 basepairs of the 5' flanking region upstream of the structural Q6 gene contain a promoter that functions as a transcription initiation site in L cells. The 3' portion of the Q6 gene appears to be responsible for the lack of cell surface expression of the intact Q6 and the hybrid Ld/Q6 genes in mouse fibroblasts. Accordingly, this portion of the Q6 class I gene may play a regulatory role in tissue-specific expression. Serological analyses of hybrid Q6 proteins suggested that Q6 may be a structural gene for CR (H-2 crossreactive) antigen found normally on subpopulations of lymphocytes. If this identification is correct, Q6 gene will define a new category of class I genes encoding approximately 40,000 mol wt molecules and carrying a characteristic truncated cytoplasmic tail. Analysis of L cells transfected with Q6 hybrid genes demonstrated also that the cytotoxic T cells specific for Qa-2a region-coded antigens recognize the amino-terminal alpha 1-alpha 2 domain of Q6 fusion products. This recognition can be blocked by anti-Qa-2a alloantiserum and monoclonal antibodies reactive with the alpha 3-beta 2-microglobulin portion of the Q6 hybrids. We propose that the structural requirements for the anti-Qa-2a cytotoxic T lymphocyte-specific epitopes on target molecules are the same as for anti-H-2-alloreactive cytotoxic T lymphocyte determinants on transplantation antigens and that the mechanism of target recognition is similar in both cases. This interpretation is consistent with the following structural similarities found in both categories of class I molecules: (a) Kd and Q6 alpha 1-alpha 2 domains share serologically defined epitopes.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Differential requirements of CD4+T-cell signals for effector cytotoxic T-lymphocyte (CTL) priming and functional memory CTL development at higher CD8+T-cell precursor frequency

Immunology ◽  
2013 ◽  
Vol 138 (4) ◽  
pp. 298-306 ◽  
Author(s):  
Channakeshava S. Umeshappa ◽  
Roopa H. Nanjundappa ◽  
Yufeng Xie ◽  
Andrew Freywald ◽  
Qingyong Xu ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Precursor ◽  
Precursor Frequency ◽  
Cell Signals

scholarly journals MHC class I antigen cross-presentation mediated by PapMV nanoparticles in human antigen-presenting cells is dependent on autophagy

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261987
Author(s):  
David Possamaï ◽  
Laïla-Aïcha Hanafi ◽  
Angélique Bellemare-Pelletier ◽  
Katia Hamelin ◽  
Paméla Thébault ◽  
...  
Keyword(s):  
Antigen Presentation ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antigen Presenting Cells ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Cross Presentation ◽  
Antigen Presenting ◽  
Papmv Nanoparticles

Nanoparticles made of the coat protein of papaya mosaic virus (PapMV) and a single-strand RNA were previously shown to be an efficient antigen presentation system for the trigger of cellular immunity. Engineering of PapMV nano with a cytotoxic T lymphocyte epitope was previously shown activating specific T lymphocytes through a proteasome-independent major histocompatibility complex class I (MHC-I) cross-presentation. In this study, we provide new insights into the mechanism of the MHC-I cross-presentation mediated by PapMV nanoparticles. We demonstrate that PapMV nanoparticles do not require the transporter associated with antigen presentation (TAP), but rather depend on lysosome acidification and cathepsin S protease activity for presentation of the T cell epitope. We have also linked the induction of autophagy with this vacuolar MHC-I cross-presentation process. Interestingly, autophagy is induced in antigen-presenting cells after PapMV nanoparticles exposure and inhibition of autophagy reduce MHC-I cross-presentation. This study demonstrates that autophagy is associated with TAP- and proteasome-independent MHC-I cross-presentation. A deeper understanding of the autophagy-dependent MHC-I cross-presentation will be useful in designing vaccination platforms that aim to trigger an efficient cytotoxic T lymphocyte response.

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