Memory T cells specific to citrullinated α-enolase are enriched in the rheumatic joint.

Journal of Autoimmunity
Jennifer PieperVivianne Malmström

Abstract

ACPA-positive rheumatoid arthritis (RA) is associated with distinct HLA-DR alleles and immune responses to many citrullinated self-antigens. Herein we investigated the T cell epitope confined within α-enolase326-340 in the context of HLA-DRB1*04:01 and assessed the corresponding CD4+ T cells in both the circulation and in the rheumatic joint. Comparative crystallographic analyses were performed for the native and citrullinated α-enolase326-340 peptides in complex with HLA-DRB1*04:01. HLA-tetramers assembled with either the native or citrullinated peptide were used for ex vivo and in vitro assessment of α-enolase-specific T cells in peripheral blood, synovial fluid and synovial tissue by flow cytometry. The native and modified peptides take a completely conserved structural conformation within the peptide-binding cleft of HLA-DRB1*04:01. The citrulline residue-327 was located N-terminally, protruding towards TCRs. The frequencies of T cells recognizing native eno326-340 were similar in synovial fluid and peripheral blood, while in contrast, the frequency of T cells recognizing cit-eno326-340 was significantly elevated in synovial fluid compared to peripheral blood (3.6-fold, p = 0.0150). Additionally, citrulline-specific T cells...Continue Reading

Citations

Apr 24, 2019·Diabetes·Anthony W PurcellTeresa P DiLorenzo
Apr 29, 2020·Nature Reviews. Rheumatology·Ashley M CurranErika Darrah
Jun 7, 2019·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Oct 1, 2020·International Journal of Molecular Sciences·Christopher SzetoStephanie Gras
Mar 27, 2021·Journal of Translational Autoimmunity·Sanjaykumar V BoddulFredrik Wermeling
Apr 14, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takahide SakuragiYasuharu Nakashima
May 4, 2021·The Journal of Clinical Investigation·Karolin WieberMichael Hertl
Jun 1, 2021·Immunological Medicine·Hisakata Yamada
Jun 11, 2021·European Journal of Immunology·Aase Hensvold, Lars Klareskog
Sep 11, 2021·HLA : Immune Response Genetics·Letícia Boslooper GonçalvesPatrícia Savio de Araujo-Souza
Feb 2, 2022·Immunological Reviews·Kathryne E Marks, Deepak A Rao

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