ISSN:0883-0185    

DOI:10.3109/08830189309061704

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Molecules of the major histocompatibility complex (MHC) were first discovered for their importance in the Rejection of tissue grafts between unrelated individuals. If these individuals differ at one or more loci within the MHC, the grafts are Rapidly Rejected. The Rejection process involves Recognition of foreign MHC molecules by T lymphocytes and the Rapid destruction by these cells of the grafted tissue cells. The MHC is a highly polymorphic complex of genes, making tissue grafting between unrelated individuals virtually impossible. Thus, it stimulated a great deal of work when organ transplantation became technically feasible.

ISSN:0883-0185    

DOI:10.3109/08830189309061705

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Antigen processing and presentation is critical to the generation and maintenance of self tolerance. The hemoglobin system has provided important data on self antigen processing and presentationin vivo.Hemoglobin/la complexes were detectable in the thymus before the time of positive and negative selection. In addition, thymic epithelial cells were shown to lack the costimulatory factors necessary to trigger T cell clone proliferation. We have extended these findings to the Renal proximal tubule. This class II MHC-expressing epithelial cell was demonstrated to process and present foreign as well as self antigens to T cell hybridomas. Current studies are examining whether this epithelial cell possesses the costimulatory factors Required to fully stimulate T cell clones, or whether the proximal tubule may play an important Role in the maintenance of self tolerance. In addition we describe the exciting model of murine autoimmune myocarditis. We have demonstrated that this is a T cell mediated disease and believe that cardiac antigen presenting cells constitutively process and present the inciting self antigen, myosin. These studies may provide important insights into autoimmunity and self tolerance.

ISSN:0883-0185    

DOI:10.3109/08830189309061706

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

For T cells,“self”is defined by the set of peptides presented on self MHC molecules at concentrations sufficient to trigger a T cell Response. A key feature of MHC molecules is their high degree of polymorphism and in the last years it has become increasingly clear that different allelic forms have different peptide specificities. Thus the set of self peptides presented (i.e.,“self”) depends on the allelic form of MHC molecules. We want to discuss here the consequences of MHC polymorphism on presentation of self peptides.

ISSN:0883-0185    

DOI:10.3109/08830189309061707

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189309061708

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Among the self antigens, immunoglobulins, and in particular idiotypes, are of special interest because of their extreme sequence heterogeneity and their postulated involvement in Regulatory interactions in the immune system. We have therefore studied antigen processing and presentation of variable Region peptides, processed idiotypes, to MHC class II molecule-restricted T cells. The immunoglobulin used has been theλ2315light chain produced by the BALB/c MOPC 315 plasmacytoma (α,λ2). The minimum length of a stimulatory synthetic idiotypic peptide comprises Residues 91-101 ofλ2315and is presented by the I-Edmolecule to CD4+T cells. T cell clones with specificity for the 91-101(X2315)/I-Edcomplex utilize a limited TCR Repertoire and are of both Th1 and Th2 type. For presentation, extracellularλ2315Requires endocytosis and processing, as previously described for conventional exogenous antigens. In addition, a B lymphoma cell can process and present its own endogenousλ2315. This was shown by transfecting manipulatedλ2315gene variants into B lymphoma cells, followed by evaluation of the APC function of the transfectants. These studies demonstrated that surface expression or secretion ofλ2315is not necessary for presentation and suggested that the endoplasmic Reticulum may be a processing compartment. To extend our findings to naive Id+B cells and anti-Id T cells, we have generatedλ2315-transgenic as well as TCR-transgenic mice. A model is presented for a T-B cell interaction based on presentation of processed idiotypes.

ISSN:0883-0185    

DOI:10.3109/08830189309061709

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Presentation of a soluble self antigen, the fifth component of complement (C5), is discussed with emphasis on the differential ability of presentation by subpopulations of APC (dendritic cells, macrophages, B cells, fibroblasts, B cell lines and bone marrow macrophages). Constitutive presentation of C5 in C5 sufficient mice is a prerequisite for tolerance induction in MHC class II restricted T cells and can be directly demonstrated by the ability of ex-vivo APC from C5 sufficient, but not C5 deficient mice, to activate C5 specific T cells in vitro in the absence of added antigen. C5 presentation and tolerance induction in MHC class II restricted T cells is strictly dependent on an exogenous source of self antigen. C5 biosynthesized, but not secreted by macrophages is ignored by MHC class II restricted cells and induces neither tolerance nor autoimmunity. C5 presentation for tolerance induction depends largely on the efficiency of antigen uptake by APC, a property which varies within different APC subpopulations and with the nature of the antigen.

ISSN:0883-0185    

DOI:10.3109/08830189309061710

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189309061711

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189309061703

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor