Validation of Shared T Cell Epitope Analysis as a Tool to Detect Preformed Donor-Reactive CD4+ Memory T-helper Cells
1Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan, 2Department of Kidney Diseases and Transplant Immunology, Aichi Medical University School of Medicine, Nagoya, Japan, 3Histocompatibility Laboratory, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan, 4Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
Meeting: 2022 American Transplant Congress
Abstract number: 929
Keywords: Antigen presentation, Epitopes, Indirect pathway, T cell reactivity
Topic: Basic Science » Basic Science » 03 - Antigen Presentation / Allorecognition / Dendritic Cells
Session Information
Session Name: Co-Stimulation in Alloreactive Effector and Regulatory Responses
Session Type: Poster Abstract
Date: Sunday, June 5, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Adaptive immunity creates immunological memory after the first response to a specific foreign antigen including HLA. During this response, adaptive immunity memorizes the molecular components known as epitope, not the foreign antigen as a whole. This memory leads to an enhanced rapid response to subsequent exposure to the same epitope and is important in organ transplantation. Recent study indicate that the presence of T-cell epitopes (TE) shared between the pre-sensitizing HLA and donor HLA evaluated by in silico assay could be a surrogate marker for diagnosing donor-reactive CD4+ memory T-helper cells (CD4+ Tmem) which would trigger an enhanced rapid adverse response to a donor organ following transplantation; however, validation of the donor-reactive CD4+ Tmem via in vitro assays has yet been done. Here we analyzed the presence of donor-reactive CD4+ Tmem which would be activated via indirect pathway using co-culturing of donor antigen-presenting recipient dendritic cells (DC) and recipient CD4+ Tmem (DC:CD4+ Tmem), and evaluate the effectiveness of shared TE analysis using in silico assay as an alternative tool to estimate donor-reactive CD4+ Tmem.
*Methods: A total of 106 adult living donor kidney transplants between 2020 and 2021 were analyzed. Pre-transplant surveillance for anti-HLA antibodies using Luminex-based assays and surveillance for shared TE using Predicted Indirectly Recognizable HLA Epitopes (PIRCHE)-II algorithm were performed. In the cohort, 11 recipients had preformed donor-specific anti-HLA antibodies (pre-DSA) and 7 recipients had shared TE. Before starting immunosuppression, DC:CD4+ Tmem was performed and IL-21 secretion from CD4+ Tmem was measured by Enzyme-Linked ImmunoSpot (ELISPOT) assay in each donor and recipient pair.
*Results: In recipients with pre-DSA, IL-21 ELISPOT count was observed significantly higher compared with no-anti HLA antibodies group (median 31 IQR(13.75-53.75) versus median 5 IQR(3-25) spots per 5 x 105 CD4 T mem, respectively; p=0.004). While in recipients with shared TE, IL-21 ELISPOT count was also observed significantly higher compared with no-anti HLA antibodies group (median 25 IQR(15-44) spots; p=0.009).
*Conclusions: These results suggest that shared TE analysis using the PIRCHE-II algorithm is effective to estimate preformed donor-reactive CD4+ Tmem, and may help to predict the risk of early deterioration of graft function.
To cite this abstract in AMA style:
Tomosugi T, Iwasaki K, Sakamoto S, Ftamura K, Okada M, Hiramitsu T, Goto N, Narumi S, Watarai Y, Kobayashi T. Validation of Shared T Cell Epitope Analysis as a Tool to Detect Preformed Donor-Reactive CD4+ Memory T-helper Cells [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/validation-of-shared-t-cell-epitope-analysis-as-a-tool-to-detect-preformed-donor-reactive-cd4-memory-t-helper-cells/. Accessed June 17, 2025.« Back to 2022 American Transplant Congress