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Minor Antigens (minor + antigen)
Selected AbstractsSensitization to Minor Antigens Is a Significant Barrier in Bone Marrow Transplantation and Is Prevented by CD154:CD40 BlockadeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010H. Xu Sensitization to major histocompatibility complex (MHC) alloantigens is critical in transplantation rejection. The mechanism of sensitization to minor histocompatibility antigens (Mi-HAg) has not been thoroughly explored. We used a mouse model of allosensitization to Mi-HAg to study the Mi-HAg sensitization barrier in bone marrow transplantation (BMT). AKR mice were sensitized with MHC congenic Mi-HAg disparate B10.BR skin grafts. Adaptive humoral (B-cells) and cellular (T cells) responses to Mi-HAg are elicited. In subsequent BMT, only 20% of sensitized mice engrafted, while 100% of unsensitized mice did. In vivo cytotoxicity assays showed that Mi-HAg sensitized AKR mice eliminated CFSE labeled donor splenocytes significantly more rapidly than naïve AKR mice but less rapidly than MHC-sensitized recipients. Sera from Mi-HAg sensitized mice also reacted with cells from other mouse strains, suggesting that Mi-HAg peptides were broadly shared between mouse strains. The production of anti-donor-Mi-HAg antibodies was totally prevented in mice treated with anti-CD154 during skin grafting, suggesting a critical role for the CD154:CD40 pathway in B-cell reactivity to Mi-HAg. Moreover, anti-CD154 treatment promoted BM engraftment to 100% in recipients previously sensitized to donor Mi-HAg. Taken together, Mi-HAg sensitization poses a significant barrier in BMT and can be overcome with CD154:CD40 costimulatory blockade. [source] A CIITA-independent pathway that promotes expression of endogenous rather than exogenous peptides in immune-privileged sitesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2004Carolina Abstract A CIITA-independent pathway of MHC class II expression has been found in the eye and the brain, both immune-privileged sites. Although corneal endothelial cells were unable to express MHC class,II in response to IFN-, alone, these cells readily expressed MHC class,II molecules via a CIITA-independent pathway when triggered by simultaneous exposure to IFN-, and TNF-,. CIITA-independent expression of MHCclass,II molecules enabled corneal endothelial cells to present cytosolic, but not endosomal, ovalbumin (OVA) to OVA-primed T,cells. To determine whether CIITA-independentexpression of MHC class,II is relevant in vivo, minor,H-only-incompatible corneal allografts prepared from CIITA knockout (KO) mice, MHC class,II KO mice or wild-type donors were placed ineyes of normal mice. Cornea allografts from wild-type and CIITA KO mice suffered similar rejection fates, whereas far fewer class,II-deficient corneas were rejected. In addition, MHC class,II-bearing macrophages were observed in cuprizone-induced inflammatory and demyelinating brain lesions of CIITA KO mice. We conclude that class,II expression via the CIITA-independent pathway enhances the vulnerability to rejection of corneal grafts expressing minor antigens. The potential relevance of CIITA-independent MHC class,II expression at immune-privileged sites is discussed in relation to tolerance to strong autoantigens. [source] Desmoglein 1 and 3 enzyme-linked immunosorbent assay in Iranian patients with pemphigus vulgaris: correlation with phenotype, severity, and disease activityJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2007M Daneshpazhooh Abstract Background, Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder of the skin and mucosa characterized by the presence of autoantibodies against desmoglein3 (Dsg3). Some patients also have antibodies against desmoglein1 (Dsg1). The aims of this study were to evaluate the diagnostic value of Dsg enzyme-linked immunosorbent assay (ELISA) in Iranian PV patients, to assess its correlation with the clinical phenotype and severity of disease and to investigate the changes of these antibodies after treatment. Methods, Seventy-three patients with PV (29 men, 44 women) presenting to the Pemphigus Research Unit at Razi Hospital, Tehran, Iran were enrolled. ELISAs were used to detect IgG autoantibodies reactive with the ectodomains of Dsg1 and Dsg3, and the correlation of antibodies with the clinical phenotype as well as oral and skin disease severity was assessed. In addition, the tests were repeated in 18 patients after treatment and the resulting remission. Results, Anti-Dsg1 and anti-Dsg3 were detected in 56 (76.7%) and 69 (94.5%) patients, respectively. Anti-Dsg1 and anti-Dsg3 antibodies were present in 48 (94.1%) and 50 (98%) patients with mucocutaneous type, in 2 (12.5%) and 15 (93.7%) patients with mucosal type, and in 6 (100%) and 4 (66.7%) patients with cutaneous PV, respectively. The mean anti-Dsg1 index values were significantly higher in cutaneous and mucocutaneous phenotypes than mucosal PV (P < 0.001). The mean anti-Dsg3 index values were significantly lower in cutaneous and mucosal phenotypes than mucocutaneous PV (P < 0.01). The severity of skin lesions (but not oral lesions) was correlated with anti-Dsg1 antibody level (P < 0.001); on the other hand, the severity of oral lesions (P < 0.01) as well as skin lesions (P < 0.001) was significantly correlated with anti-Dsg3 antibody levels. Both anti-Dsg1 and anti-Dsg3 levels were significantly reduced after treatment and clinical remission (P < 0.001). Conclusion,, Dsg ELISA is not only a sensitive tool for the diagnosis of PV, it can also serve as a predictive means for assessing the severity as well as for monitoring the disease activity. Although, in general, the clinical phenotype is related to the antibody profile, there are occasional cases with discordant phenotype and antibody profile. These discrepancies might be explained by genetic variations or the presence of possible minor antigens involved in the pathogenesis of pemphigus. [source] REVIEW ARTICLE: Tolerance Mechanisms in Pregnancy: A Reappraisal of the Role of Class I Paternal MHC Antigens,AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010David A. Clark Citation Clark DA, Chaouat G, Wong K, Gorczynski RM, Kinsky R. Tolerance mechanisms in pregnancy: a reappraisal of the role of class I paternal MHC antigens. Am J Reprod Immunol 2010; 63: 93,103 Problem, Allogeneic pregnancies have a survival advantage over syngeneic pregnancies, and paternal Class I MHC antigens have been implicated. In humans, HLA-C and HLA-G and E are expressed by subpopulations of fetal trophoblast. In mice, Qa-2, a Class Ib antigen, and classical H-2K antigens have been described. However, the mechanism of prevention of embryo demise in utero has not been critically assessed, and a number of conflicting ideas have not been addressed. The ,, T-cell receptor recognizes peptide bound to the groove in Class I MHC, and peptides have profound effects on the interaction of KIR receptors on T and NK cells with Class I MHC. Methods, Data on prevention of pregnancy loss (abortion) in poly IC-treated mice were reviewed along with information about prevention of losses in the abortion-prone CBA × DBA/2 model. This information was combined with data on paternal antigen expression at different times in pregnancy when key events determining outcome are thought to transpire, and role of tolerance signaling molecules such as CD200. Current data on models supporting a role for ,true' uterine NK cells (TuNKs) versus blood NK cells in the uterus (BuNKs) and role of MHC,KIR interaction were reviewed along with incompatible data in the literature. Results, Whilst paternal Class I MHC appears important, there is an important role for paternal non-MHC minor antigens (small peptides) that bind to the antigen-presenting groove of Class I MHC. BuNKs along with CD8+ T cells and Treg cells appear more important than TuNKs where the role of the latter appears primarily to promote angiogenesis. When during pregnancy the maternal immune system cells are first exposed to paternal Class I + peptide is uncertain, but at the time of implantation, if not earlier, seems likely. Conclusion, Suppression of pregnancy loss by paternal/embryo Class I MHC depends on the presence of paternal peptides. This greatly complicates existing models of Class I,KIR interactions in feto-maternal tolerance or rejection. It is important to consider all the data when devising explanatory models. [source] | ||||||||||