Cutting Edge: Unique T Cells That Recognize Citrullinated Peptides Are a Feature of Protein Immunization

Abstract

Abs against citrullinated proteins are present in patients with rheumatoid arthritis. In this study, we describe a unique cohort of T cells that selectively responded to citrullinated variants of two epitopes of hen egg-white lysozyme, a major and a minor one, bound to the MHC molecule, I-Ak. In addition, we show that when given an intact, unmodified lysozyme protein, dendritic cells and peritoneal macrophages presented citrullinated peptides and stimulated modification-specific T cells. Thus, presentation of citrullinated-peptide-MHC complex is a feature of immune responses to protein Ags.

Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells

“…PAD2 and PAD4 are expressed in APCs, but PAD4 was shown to be expressed at lower levels in C3.F6 and B cells (Vossenaar et al, 2004;Ireland et al, 2006). Quantitation of PAD2 and PAD4 mRNA in the various APCs examined in this study confirmed these findings (Fig.…”

“…We previously reported that immunization with the protein hen egg-white lysozyme (HEL) gave rise to T cells that recognized different sets of HEL peptides presented by class II MHC molecules (Ireland et al, 2006). In this study, we correlate the response of a T cell that exclusively recognizes the chemically dominant HEL peptide, 48-62 (DGSTDYGILQINSRW), with a citrulline to arginine change at residue 61 to autophagy.…”

“…Serum starvation induces presentation of citrullinated peptides by B lymphoma cells To determine the reasons for the lack of citrullination by B cells and explore conditions that may induce it, we examined C3.F6, a B lymphoma line which when cultured with HEL does not present the 48-62-Cit61 peptide (Ireland et al, 2006). We examined in particular C3.F6.mHEL that expresses HEL with a transmembrane linker and constitutively presents high levels of HEL peptides on I-A k molecules.…”

Emerging patterns of risk factor make‐up enable subclassification of rheumatoid arthritis

“…Unfortunately, this so-called SE hypothesis has not yet been confirmed by the identification of specific arthritogenic peptides that bind to the HLA-DR proteins in RA. Nevertheless, it has been suggested that citrullination could allow the binding of certain peptides to the HLA SE molecules (25,26), and that the association of the SE alleles with RA (although quantitatively varying between alleles and populations) is robust because of its consistent association with disease susceptibility and severity among varied ethnic populations.…”

HLA and Citrullinated Peptides in Rheumatoid Arthritis

“…Concretely, HEL was used as a model antigen, and T cells specifically reactive to citrullinated epitopes were detected among the responding repertoire to immunization with an unmodified HEL protein. In addition, antigen presenting cells (APCs), including dendritic cells and peritoneal macrophages, were able to present citrullinated peptides when provided an intact, unmodified HEL ex vivo (Ireland et al, 2006). Therefore, APCs were capable to capture and process the antigen, to deiminate some specific arginine residues and to present some citrullin-containing peptides to T cells in a correct way to induce an specific response against citrullinated peptides.…”