Epitope Analysis of Hla Class I Donor Specific Antibodies in Sensitized Renal Transplant Recipients

Papassavas, Andreas; Iniotaki-Theodoraki, A; Boletis, John; Kostakis, A.; Stavropoulos-Giokas, Catherine

doi:10.1097/00007890-200007270-00016

Cited by 20 publications

(11 citation statements)

References 17 publications

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“…It is important to emphasize that the FlowPRA class I Single Antigen technique allowed us to identify most of the antibodies specific for antigens sharing the same immunizing epitopes in each serum sample. Contrary to a recent report (18), our study showed that only five of the 55 (9%) anti-HLA class I-positive patients developed alloantibodies with specificity restricted to the mismatched HLA-A or -B antigen/s of the graft, that is to say alloantibodies specific for the "private" epitopes of the mismatched donor HLA class I molecules. A broad HLA-A and/or -B sensitization was found in more than 90% of the study population.…”

Section: Discussioncontrasting

confidence: 99%

Public Epitope Specificity of HLA Class I Antibodies Induced by a Failed Kidney Transplant: Alloantibody Characterization by Flow Cytometric Techniques

et al. 2006

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Section: Discussioncontrasting

confidence: 99%

Public Epitope Specificity of HLA Class I Antibodies Induced by a Failed Kidney Transplant: Alloantibody Characterization by Flow Cytometric Techniques

et al. 2006

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“…In contrast, 3-83 B cells, alloantibodies, and immune complexes are more likely to enhance T cell activation through the indirect presentation pathway in vivo. We therefore theorize that the increased frequency of allospecific T cells observed in the ELISPOT assay reflects not only alloreactive T cells that were activated via the indirect pathway, but also alloreactive T cells that become activated by the direct pathway; these cells may have become activated by the process of epitope spreading (55) or by the semidirect pathway described by Lechler and colleagues (56).…”

Section: Discussionmentioning

confidence: 98%

Memory Alloreactive B Cells and Alloantibodies Prevent Anti-CD154-Mediated Allograft Acceptance

Burns

et al. 2009

The Journal of Immunology

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The impact of memory B cells and alloantibodies on the ability to induce transplantation tolerance has not been elucidated. We have developed a murine heart transplant model that isolates the contributions of functional memory B cells from memory T cells in allograft rejection. Memory 3-83 B cells with dual specificity for H-2Kk and H-2Kb were generated in 3-83 Igi BCR knockin (BALB/c background) mice by the transplantation of C3H (H-2Kk) hearts in the absence of immunosuppression. To test the effect of functional memory 3-83 B cells, C3H-primed 3-83 Igi recipients were challenged with C57BL/6 hearts (H-2Kb) at 60–90 days post-C3H heart transplant and treated with anti-CD154 mAbs. Despite immunosuppression, the C57BL/6 hearts were acutely rejected within 10–13 days and graft rejection was associated with increased frequencies of C57BL/6-specific IFN-γ-producing T cells. Histology revealed significant numbers of infiltrating T cells, consistent with acute T cell-mediated rejection. The resistance to tolerance induction was dependent on the synergistic effects of memory 3-83 B cells and alloantibodies, whereas memory T cells are not necessary. We conclude that the combined effects of functional memory B cells and alloantibodies prevent anti-CD154-mediated graft acceptance by facilitating the CD40-CD154-independent activation of alloreactive T cells. This study provides insight into the potential ability of memory B cells and alloantibodies to prevent anti-CD154-mediated graft acceptance.

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“…A consensus is emerging that donor-specific Abs (DSAs) are predictive of poor graft outcome (30,31), and the activation of complement downstream of DSA binding to graft endothelium comprises the currently accepted paradigm for the mechanistic basis of how DSA effects graft loss (32). The observations in this study challenge the limited scope of this paradigm and demonstrate the ability of alloantibodies to function as opsonins to facilitate CD40-CD154-independent T cell activation and the rejection of allogeneic heart and skin grafts.…”

Section: Discussionmentioning

confidence: 99%

Alloantibodies Prevent the Induction of Transplantation Tolerance by Enhancing Alloreactive T Cell Priming

Burns

Chong

2011

The Journal of Immunology

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Circulating alloantibodies in transplant recipients are often associated with increased Ab-mediated as well as cellular rejection. We tested the hypothesis that alloantibodies facilitate cellular rejection by functioning as opsonins to enhance T cell activation using a BALB/c to C57BL/6 heart or skin transplant model. Long-term heart and skin survival induced with anti-CD154 alone or in combination with donor-specific transfusion (DST), respectively, was abrogated by the presence of anti-Kd mAbs, and alloreactive T cell activation as well as acute rejection was observed. The prevention of graft acceptance in the skin model was dependent on anti-Kd binding to and converting DST from tolerigenic to immunogenic. Adoptive transfer of CFSE-labeled TCR-transgenic T cells into B6 recipients treated with anti-CD154/DST revealed the ability of anti-Kd to enhance the proliferation of anti–Kd-specific T cells via the indirect pathway as well as of non–Kd-reactive, recipient MHC-restricted CD4+ and CD8+ T cells. Thus, alloantibodies with restricted specificity are able to facilitate the indirect presentation as well as the cross-presentation of a larger repertoire of “linked” donor-derived Ags. These observations highlight the ability of alloantibodies to function not only in classical humoral rejection but also as opsonins that facilitate the CD40-CD154–independent activation of alloreactive T cells.

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Epitope Analysis of Hla Class I Donor Specific Antibodies in Sensitized Renal Transplant Recipients

Cited by 20 publications

References 17 publications

Public Epitope Specificity of HLA Class I Antibodies Induced by a Failed Kidney Transplant: Alloantibody Characterization by Flow Cytometric Techniques

Public Epitope Specificity of HLA Class I Antibodies Induced by a Failed Kidney Transplant: Alloantibody Characterization by Flow Cytometric Techniques

Memory Alloreactive B Cells and Alloantibodies Prevent Anti-CD154-Mediated Allograft Acceptance

Alloantibodies Prevent the Induction of Transplantation Tolerance by Enhancing Alloreactive T Cell Priming

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