PEPTIDES DERIVED FROM Α-Helices OF ALLOGENEIC CLASS I MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS ARE POTENT INDUCERS OF CD4+ AND CD8+ T CELL AND B CELL RESPONSES AFTER CARDIAC ALLOGRAFT REJECTION

Shirwan, Haval; LEAMER, MICHAELA; Wang, Hong K.; Makowka, Leonard; Cramer, Donald V.

doi:10.1097/00007890-199502150-00016

Cited by 32 publications

(10 citation statements)

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“…1W heart rejection as early as day 5 after transplantation for peptide 29 and day seven for peptides 37 and 38. Testing of purified CD4 + or CD8 + subsets revealed that the responses toward peptides 29 and 37 were CD4 + and CD8 + -mediated, respectively. Several studies have previously shown that indirectly primed T cells are involved in allograft rejection in many experimental models (23)(24)(25)(26) and in humans (27,28). We have also shown that in the same strain combination, LEW.…”

Section: Discussionmentioning

confidence: 99%

Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Ballet

Renaudin

Degauque

et al. 2009

American Journal of Transplantation

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Priming of recipients by DST induces long-term survival of mismatched allografts in adult rats. Despite these recipients developing inducible T regulatory cells able to transfer long-term graft survival to a secondary host, a state of chronic rejection is also observed. We revisited the molecular donor MHC targets of the cellular response in acute rejection and analyzed the cellular and humoral responses in recipients with long-term graft survival following transplantation. We found three immunodominant peptides, all derived from LEW.1W RT1.D u molecules to be involved in acute rejection of grafts from unmodified LEW.1A recipients. Although the direct pathway of allorecognition was reduced in DST-treated recipients, the early CD4 + indirect pathway response to dominant peptides was almost unimpaired. We also detected early and sustained antidonor class I and II antibody subtypes with diffuse C4d deposits on graft vessels. Finally, long-term accepted grafts displayed leukocyte infiltration, endarteritis and fibrosis, which evolved toward vascular narrowing at day 100. Altogether, these data suggest that the chronic graft lesions developed in long-term graft recipients are the result of progressive humoral injury associated with a persisting indirect T helper response. These features may represent a useful model for understanding and manipulating chronic active antibodymediated rejection in human.

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Section: Discussionmentioning

confidence: 99%

Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Ballet

Renaudin

Degauque

et al. 2009

American Journal of Transplantation

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“…Intra-abdominal heterotopic heart transplantation was performed using C57BL/10 (B10) male mice as recipients of cardiac xenografts of 12 to 15-daysold PVG.R8 male rats under anesthesia [13]. Heart contractions were assessed daily by palpation and rejection was defined as the day of cessation of heartbeat.…”

Section: Heterotopic Cardiac Transplantationmentioning

confidence: 99%

“…Splenocytes or lymph node cells of naive or transplanted recipients at rejection were used as responders in a standard MLR assay [13]. In brief, single cell suspension was prepared from spleens or mesenteric lymph nodes in complete MLR medium consisting of Dulbecco's modified Eagle's medium (DMEM) supplemented with 1 mM sodium pyruvate, 10 mM N-2-Hydroxyethylpiperazine-N-2-Ethane Sulfonic Acid (HEPES), 100 U/ml penicillin and 100 lg/ml streptomycin, 4 mM l-arginine, 1.36 mM folic acid, 50 lM 2-b mercaptoethanol, l2 mM l-glutamine, 5% fetal bovine serum, and 1% responder serum.…”

Section: Proliferation Assaymentioning

confidence: 99%

“…These results demonstrate that indirect recognition mediated by CD4 + T cells plays a critical role in the rejection of cardiac grafts in the rat-to-mouse xenogeneic model. recognition) [12][13][14][15]. The direct recognition pathway stimulates a high precursor frequency of T cells that elicit effector mechanisms of acute graft rejection [10,11,[13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

“…recognition) [12][13][14][15]. The direct recognition pathway stimulates a high precursor frequency of T cells that elicit effector mechanisms of acute graft rejection [10,11,[13][14][15][16][17][18]. The indirect recognition of MHC molecules and minor histocompatibility antigens by T cells, on the other hand, initiates more subdued immune responses that may be critical to chronic allograft rejection [11,[19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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Blockade of indirect recognition mediated by CD4⁺ T cells leads to prolonged cardiac xenograft survival

Singh

Guo

Que

et al. 2003

Xenotransplantation

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The T-cell response to xenografts is induced by direct and indirect recognition of xenoantigens. Although the importance of indirect recognition is well established in vitro, the contribution of this pathway to xenograft rejection in vivo remains to be fully elucidated. We herein investigated the direct contribution of indirect recognition to cardiac xenograft rejection in the rat-to-mouse (PVG.R8-to-C57BL/10) concordant model. Rat xenoantigens invoked a vigorous proliferative response in mouse T cells harvested from naïve or graft recipients at rejection. Indirect recognition predominated the response, as antibodies against mouse class II I-A(b), CD80, or CD86 molecules significantly (45 to 60%) blocked the proliferative response. Importantly, the blockade of indirect recognition in vivo by treating the graft recipients with a monoclonal antibody (mAb) against class II I-A(b) molecule on days 0, 1, and 3 post-transplantation resulted in significant (P < 0.009) prolongation of cardiac xenograft survival (Mean Survival Time (MST) >94 +/- 55 days vs. 7 +/- 0.8 days for controls). In contrast, treatment of recipients with a mAb against mouse class I H-2K(b)/D(b) molecules did not significantly affect graft rejection (MST = 8 +/- 1 days). These results demonstrate that indirect recognition mediated by CD4(+) T cells plays a critical role in the rejection of cardiac grafts in the rat-to-mouse xenogeneic model.

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Differential geometric analysis of alterations in MH α‐helices

et al. 2013

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Antigen presenting cells present processed peptides via their major histocompatibility (MH) complex to the T cell receptors (TRs) of T cells. If a peptide is immunogenic, a signaling cascade can be triggered within the T cell. However, the binding of different peptides and/or different TRs to MH is also known to influence the spatial arrangement of the MH α-helices which could itself be an additional level of T cell regulation. In this study, we introduce a new methodology based on differential geometric parameters to describe MH deformations in a detailed and comparable way. For this purpose, we represent MH α-helices by curves. On the basis of these curves, we calculate in a first step the curvature and torsion to describe each α-helix independently. In a second step, we calculate the distribution parameter and the conical curvature of the ruled surface to describe the relative orientation of the two α-helices. On the basis of four different test sets, we show how these differential geometric parameters can be used to describe changes in the spatial arrangement of the MH α-helices for different biological challenges. In the first test set, we illustrate on the basis of all available crystal structures for (TR)/pMH complexes how the binding of TRs influences the MH helices. In the second test set, we show a cross evaluation of different MH alleles with the same peptide and the same MH allele with different peptides. In the third test set, we present the spatial effects of different TRs on the same peptide/MH complex. In the fourth test set, we illustrate how a severe conformational change in an α-helix can be described quantitatively. Taken together, we provide a novel structural methodology to numerically describe subtle and severe alterations in MH α-helices for a broad range of applications. © 2013 Wiley Periodicals, Inc.

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PEPTIDES DERIVED FROM Α-Helices OF ALLOGENEIC CLASS I MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS ARE POTENT INDUCERS OF CD4+ AND CD8+ T CELL AND B CELL RESPONSES AFTER CARDIAC ALLOGRAFT REJECTION

Cited by 32 publications

References 0 publications

Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Blockade of indirect recognition mediated by CD4⁺ T cells leads to prolonged cardiac xenograft survival

Differential geometric analysis of alterations in MH α‐helices

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PEPTIDES DERIVED FROM Α-Helices OF ALLOGENEIC CLASS I MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS ARE POTENT INDUCERS OF CD4+ AND CD8+ T CELL AND B CELL RESPONSES AFTER CARDIAC ALLOGRAFT REJECTION

Cited by 32 publications

References 0 publications

Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Blockade of indirect recognition mediated by CD4+ T cells leads to prolonged cardiac xenograft survival

Differential geometric analysis of alterations in MH α‐helices

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Blockade of indirect recognition mediated by CD4⁺ T cells leads to prolonged cardiac xenograft survival