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MHC Antigens (mhc + antigen)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

REVIEW ARTICLE: Tolerance Mechanisms in Pregnancy: A Reappraisal of the Role of Class I Paternal MHC Antigens,

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010
David 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]

The effects of gp100 and tyrosinase peptide vaccinations on nevi in melanoma patients

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2006
David S. Cassarino
Background:, A new approach to prevent disease recurrence in high-risk melanoma patients involves immunization with gp100 and tyrosinase peptides. This is the first study to examine the effects of such treatments on nevi. Design:, We studied biopsies of ,clinically atypical' nevi from 10 patients before and after peptide vaccination. All had a cutaneous melanoma measuring at least 1.5 mm in depth, satellite metastases, or at least one positive lymph node. We performed immunohistochemical stains for CD3, CD4, CD8, MHC-I, MHC-II, CD1a, HMB-45, MART-1, tyrosinase, bcl-2, p53, and Ki-67 (mib-1). Results:, Immunohistochemistry showed no differences in staining due to vaccination in either the immunologic or melanocytic markers. However, there was a significant increase in both p53 and bcl-2 staining, and a trend toward decreased Ki-67 staining, in the nevi post-treatment. Discussion:, The primary goal of peptide vaccinations with gp100 and tyrosinase is to activate melanoma-specific T cells in order to prevent melanoma recurrence. Nevi were studied in order to assess the effects on benign melanocytes. No significant changes in lymphocytes, langerhans cells, expression of MHC antigens, or melanocytic markers were found. The increase in p53 and bcl-2 raises the possibility that vaccination with melanocytic antigens stimulates a response in benign melanocytes. [source]

REVIEW ARTICLE: Tolerance Mechanisms in Pregnancy: A Reappraisal of the Role of Class I Paternal MHC Antigens,

ORIGINAL ARTICLE: Syngeneic Immune-Dependent Abortions in Mice Suggest Paternal Alloantigen-Independent Mechanisms

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2008
Jean A. Kundert
Problem, Recurrent immune-associated miscarriages in humans are thought to result from maternal immune responses to paternal alloantigens. We investigated the role of paternal alloantigens in a mouse model of immune-dependent abortion. Method of study, Sib-crosses of C57Bl/6J (haplotype b/b) mice heterozygous for a targeted hypomorphic allele of the tbp gene (tbp,,/+) resulted in selective mid-gestational abortion of 88% of the tbp,,/,, fetuses. In dams lacking mature lymphocytes (rag1,/,), nearly all tbp,,/,, fetuses survived to birth, indicating abortions were immune-dependent. Allogeneic pregnancies bearing tbp,,/,, fetuses were established by either hybridizing the paternal lineage to BALB/cJ (haplotype d/d) and mating hybrid tbp,,/+ sires to haplotype b/b tbp,,/+ C57Bl/6J dams, or by transfer of haplotype b/b zygotes from tbp,,/+ × tbp,,/+ matings into pseudopregnant wild-type CByD2F1/J dams (haplotype d/d). Results, Neither hemizygous paternal allogeneic loci nor homozygous allogeneic loci, including a haplotype-mismatched major histocompatibility complex (MHC), increased abortion frequencies. Conclusion, Results suggested that mechanisms for maternal tolerance of paternal alloantigens, including mismatched MHC antigens, were intact in these pregnancies, yet maternal immune-dependent paternal antigen-independent abortion of mutants occurred. These data indicate that, in some cases of immune-mediated abortions, the presence of paternal alloantigens can be coincidental and superfluous to the compromising rejection response. [source]

Complement Independent Antibody-Mediated Endarteritis and Transplant Arteriopathy in Mice

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010
T. Hirohashi
Complement fixation, as evidenced by C4d in the microvasculature, is a widely accepted criterion of antibody-mediated rejection. Complement fixation has been shown to be essential in acute antibody-mediated rejection, but its role in chronic rejection has not been addressed. Previous studies showed that passive transfer of complement fixing monoclonal IgG2a anti-H-2Kk into B6.RAG1,/, KO recipients of B10.BR hearts led to progressive chronic transplant arteriopathy (CTA) over 14,28 days, accompanied by C4d deposition. The present studies were designed to test whether complement was required for these lesions. We report that a noncomplement fixing donor-specific alloantibody (DSA, monoclonal IgG1 anti-H-2Kk) injected into B6.RAG1 -/- KO recipients of B10.BR hearts also promotes CTA, without C4d deposition. Furthermore, a passive transfer of DSA (monoclonal IgG2a anti-H-2Kk) initiated endarteritis followed by CTA in B6.RAG1,/- mice genetically deficient in the third component of complement (RAG1,/,C3,/,). These studies indicate that antibody to class I MHC antigens can trigger chronic arterial lesions in vivo without complement participation, in contrast to acute antibody-mediated rejection. This pathway may be relevant to C4d-negative chronic rejection sometimes observed in patients with DSA, and argues that lack of C4d deposition does not exclude antibody-mediated chronic rejection. [source]

IK cytokine ameliorates the progression of lupus nephritis in MRL/lpr mice

ARTHRITIS & RHEUMATISM, Issue 11 2006
Masatake Muraoka
Objective IK cytokine has been isolated as a factor that inhibits interferon-, (IFN,),induced expression of class II major histocompatibility complex (MHC) antigens. Aberrant expression of class II MHC antigens has reportedly been recognized in the target organs of autoimmune diseases and been associated with disease activity. In this study, we investigated whether IK cytokine can ameliorate the progression of lupus nephritis in MRL/lpr mice. Methods A truncated IK analog was prepared and transfected into a nonmetastatic fibroblastoid cell line, and then injected subcutaneously into MRL/lpr mice at ages 8 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease). Results An IK cytokine, when it was translated from methionine at position 316, acted as a secretory protein. This truncated IK cytokine (tIK) reduced IFN,-induced class II MHC expression in various cells through decreased expression of class II MHC transcription activator. Treatment of MRL/lpr mice with tIK significantly reduced renal damage as compared with control mice. A significant decrease in macrophage and T cell infiltration was found in the kidneys of tIK-treated mice, resulting in decreased production of IFN, and interleukin-2. Mice treated with tIK also showed significant reduction of anti-DNA antibodies and circulating immune complexes. A specific reduction of class II MHC expression was observed on B cells and monocytes as well as in the kidney. Conclusion We prepared a potent IK analog and demonstrated its ability to ameliorate the progression of lupus nephritis. This agent may therefore provide a new therapeutic approach for lupus nephritis. [source]

Human cytomegalovirus induces a direct inhibitory effect on antigen presentation by monocyte-derived immature dendritic cells

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2002
Ulrich Grigoleit
Summary. The hypothesis that productive infection of monocyte-derived immature dendritic cells (DCs) by the human cytomegalovirus (HCMV) is associated with decreased immunostimulatory capacity was tested in this study. DCs were infected with 60,80% efficiency by HCMV strain TB40/E. Infected versus uninfected cells were analysed by fluorescence-activated cell sorting and by immunocytochemistry for surface expression of major histocompatibility complex (MHC) and co-stimulatory molecules as well as cytokine secretion during the 3 d after infection. The immunostimulatory capacity of these cells was measured by mixed leucocyte reaction. In spite of the fact that HCMV infection of DCs induced an increased release of tumour necrosis factor-, (TNF-,) and a decreased interleukin 10 (IL-10) production, expression of MHC class I and II, as well as CD40 and CD80 molecules, were downregulated on infected DCs. The mixed leucocyte reaction showed significantly reduced immunostimulatory capacity of infected DC cultures. Simultaneous detection of MHC antigens and virus antigens by double immunofluorescence revealed that downregulation occurred only on infected cells, but not on uninfected bystander cells. These findings demonstrate on a single cell level, together with the marked downregulation of MHC and co-stimulatory molecules in the presence of high TNF-, and low IL-10 levels, a direct inhibitory effect of HCMV on antigen presentation by immature DCs independent of soluble mediators. [source]