Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice

Abstract

IntroductionThe immune system responds to invading pathogens by recognizing their antigenic structures, while remaining unresponsive to self antigens. This simplified model, however, is challenged by the understanding that autoreactivity is a common feature of healthy organisms and a part of peripheral tolerance mechanisms. To generate animal models for autoimmune diseases, susceptible species are often immunized with self antigens. However, not all immunogenic self antigens have the capacity to provoke a pathogenic autoimmune response, and some of them confer protection (1). A widely accepted animal model for human rheumatoid arthritis is collageninduced arthritis (CIA) in mice. CIA is induced by immunizing susceptible mouse strains with cartilage-derived triple helical type II collagen (CII). In mice expressing the MHC class II molecule H-2A q , the disease-mediating epitope is an immunodominant glycopeptide derived from position 260-270 of rat CII (2). In comparison with heterologous CII, mouse CII, although capable of inducing arthritis, provokes a much weaker immune response to the immunodominant epitope and induces a lower incidence of arthritis (3). However, mouse CII immunization induces a recall proliferative response toward multiple epitopes in addition to the MHC class II-restricted CII 260-270 peptide (4). The major epitopes share a common motif, with the strongest located at position 707-721 (mCII [707][708][709][710][711][712][713][714][715][716][717][718][719][720][721] ). By investigating the immune response to this epitope, surprisingly, we found that this peptide was not MHC I/II restricted, but was binding and presented by CD1d, a cluster of

Mechanisms and Consequences of Antigen Presentation by CD1

“…However, due to difficulties in understanding the molecular basis of peptide recognition and the preponderance of lipid-reactivity among CD1d-restricted T cells, the issue of peptide-reactivity was largely put to rest. A more recent study reported CD1d-restricted recognition of a collagen-derived peptide by CD4 + T cells [102], but its molecular basis was unclear. Until the recent study by Girardi et al .…”

“…Although the functions of peptide-reactive dNKT cells remain to be determined, it is striking that the CD1d peptide motif is contained within peptides derived from several viruses such as HIV [103], suggesting potential anti-viral functions. Additionally, studies with the CD1d-binding, collagen-derived peptide have provided evidence for potent immune modulatory activities of peptide-reactive, CD1d-restricted T cells [102]. …”

Invariant Natural Killer T Cells in Rheumatoid Arthritis and Other Inflammatory Arthritides

“…SGL-S23 also suppressed histamine release, and more effectively so than α-GalCer or high dose IFN-. Finally, CIA suppression through NKT cell manipulation can be accomplished with nonglycolipid stimulation as shown by Liu et al (2011). Immunisation with murine CII induces a weaker responsethan heterologous collagen, characterised by multiple epitopes sharing a common motif, the strongest located at position 707-721.…”

NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

“…NKT cells are a subgroup of T-cells, which express the NK cell surface marker NK1.1 and a restricted TCR repertoire recognizing glycolipids and self-peptides presented by the major histocompatibility complex class 1-related glycoprotein CD1d (Fowlkes et al, 1987;Makino et al, 1995;Issazadeh-Navikas, 2012;Liu et al, 2011a). Besides being expressed on professional APCs a recent report has shown that CD1d is also expressed on epithelial cells in the human vagina (Kawana et al, 2008).…”