Soluble major histocompatibility complex molecules in immune regulation: highlighting class II antigens

Abstract

SummaryThe involvement of major histocompatibility complex (MHC) antigens in the development and regulation of immune response has been well defined over the years, starting from maturation, antigenic peptide loading, migration to the cell membrane for recognition by the T-cell receptor and recycling for immune response cessation. During this intracellular trafficking, MHC antigens find a way to be excreted by the cells, because they can be found as soluble MHC class I (sMHC-I) and class II (sMHC-II) molecules in all body fluids. Although secretion mechanisms have not been sufficiently studied, sMHC molecules have been shown to display important immunoregulatory properties. Their levels in the serum have been shown to be altered in a variety of diseases, including viral infections, inflammation, autoimmunities and cancer, etc. while they seem to be involved in a number of physiological reactions, including maintenance of tolerance, reproduction, as well as mate choice vis-a-vis species evolution. The present review aims to present the thus far existing literature on sMHC molecules and point out the importance of these molecules in the maintenance of immune homeostasis.

Soluble HLA-I and HLA-II Molecules Are Potential Prognostic Markers of Progression of Systemic and Local Inflammation in Patients with COPD

“…Significant amounts of sHLA-I and sHLA-II molecules are produced by various activated cells of the immune system under the influence of mitogens and various antigens [12–14]. Thus, the content of sHLA-I and sHLA-II can reflect the functional state of cellular immunity.…”

Rescue of autoimmune hepatitis by soluble MHC class II molecules in an altered concanavalin A‐induced experimental model

“…As mentioned in the introduction, sMHCII proteins are loaded with self/tolerogenic antigenic epitopes, maintaining thus tolerance by blocking autoreactive T-cell activation. 21,22 Indeed, sMHCII molecules isolated from healthy/normal mice have revealed by mass spectroscopy analysis more than 600 self-antigenic epitopes. 22 Within that list of antigenic epitopes, one recognizes small nuclear ribonucleoprotein-associated protein B, ribonucleoprotein A, isoform 2 of spectrin alpha chain, myosin-9, myosin light chain, lamin-A, anti-mitochondrial autoantigens, stress-70 protein, all of which are being recognized as autoantigens in a variety of AIH patients.…”

“…Autoimmune hepatitis (AIH) is a severe autoimmune condition manifested by chronic liver inflammation leading to fibrosis and eventually necrosis. Among the several experimental animal models described in the literature, the present study concentrated on an inducible by ConA model of BALB/c mice, which has been shown to display most of the pathologic symptoms observed in humans 9,10 and attempted to rescue the AIH phenotype by sMHCII molecules, which as previously shown play an important role in maintaining tolerance to the organism 21 . The results presented herein showed that indeed, serum‐isolated syngeneic sMHCII molecules could rapidly reverse all serologic and cellular markers tested to control levels, while alleviating in the long term the pathologic AIH phenotype.…”

“…Recent observations indicate that soluble major histocompatibility complex class II (sMHCII) molecules found in serum and body fluids of healthy individuals, among their other properties, play an important role in maintaining tolerance. 21 In particular, sMHCII molecules are proteins of approximately 60 kD that appear to compete with membrane MHCII for T-cell receptor (TCR) binding, leading to preclusion of T-cell activation and interception of inflammatory cytokine production, thus, driving the immune system toward suppression. Self-tolerance is believed to be mediated by sMHCII molecules loaded with self-antigens, which bind to the TCR of autoreactive T lymphocytes leading to suppression and the overall protection from autoimmunity.…”

An Antibody Specific for the Dog Leukocyte Antigen DR (DLA-DR) and Its Novel Methotrexate Conjugate Inhibit the Growth of Canine B Cell Lymphoma

“…Various strategies of tumor survival could account for the observed variations in sHLA-DR. We speculate that, on the one hand, melanoma cells could down-modulate HLA-DR expression in order to counteract recognition by tumor-specific effector T cells. On the other hand, a massive release of sHLA-DR by B cell neoplasms might induce tolerogenic T cell responses, which could weaken tumor immune-surveillance [24,36]. In order to assess the levels of soluble, circulating DLA-DR molecules (sDLA-DR) in the blood of tumor-bearing NOD-SCID mice undergoing experimental therapy with B5 and B5-MTX, we devised an immune-enzymatic assay based on the use of two species-specific mAbs recognizing different and non-overlapping epitopes of DLA-DR (B5 and E11) [19].…”