Kidney Week

Abstract: PO1779

T-Cell Epitopes of M-Type Transmembrane Phospholipase A2 Receptor in Primary Membranous Nephropathy

Session Information

• Glomerular Diseases: Lupus and Membranous
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Zhang, Xiao-dan, Peking University First Hospital Department of Nephrology, Beijing, Beijing, China

Xiao-dan Zhang,

• Zhao, Cui, Peking University First Hospital Department of Nephrology, Beijing, Beijing, China

Cui Zhao,

Background

PLA2R is the major autoantigen of pMN. There is no information on T cell epitopes. We previously identified the risk HLA molecules DRB1*1501 and DRB1*0301.

Methods

123 linear peptides, each consisting of 15-22 amino acids and overlapping by 8-12 amino acids, were synthesized across PLA2R. Their binding capacity to DRB1*1501 and DRB1*0301 were assessed by flow cytometry. Proliferation of CD4⁺ T cells from patients with anti-PLA2R positive pMN was analyzed after peptide stimulation using CFSE dilution assay. Cytokines produced by activated PBMC were measured by cytometric beads array.

Results

We found 17 peptides that bound to both DRB1*1501 and DRB1*0301 molecules with high capacity. Among them, 11 peptides induced significant proliferations of CD4⁺ T cells from patients with anti-PLA2R positive pMN: PLA2R_38-52(CysR1), PLA2R_52-66(CysR3), PLA2R_101-120(CysR10), PLA2R_113-129(CysR12), PLA2R_193-212(FnII-3), PLA2R_602-621(CTLD3-9), PLA2R_612-631(CTLD3-10), PLA2R_622-641(CTLD3-11), PLA2R_829-838(CTLD5-2-1), PLA2R_1121-1140(CTLD7-1) and PLA2R_1129-1150(CTLD7-2). Upon activation, PBMCs had similar pro-inflammatory cytokine profiles, predominantly IL-6, TNF-α and IL-10, and to a lesser extent IL-4/5/13 and IL-17.

Conclusion

Thus, we identified 11 potential T-cell epitopes on PLA2R.