scholarly journals Suppressive effect of antibody on processing of T cell epitopes.

1993 ◽  
Vol 178 (4) ◽  
pp. 1459-1463 ◽  
Author(s):  
C Watts ◽  
A Lanzavecchia
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Suppressive Effect ◽  
T Cell Epitopes ◽  
Strong Suppression ◽  
Lysosomal Ph ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Formed Part ◽  
Antigen Presenting

Immunoglobulins drive efficient antigen capture by antigen presenting cells for processing and presentation on class II MHC-molecules. High affinity antibody/antigen interactions are stable at endosomal/lysosomal pH thus altering the substrate for antigen processing. We show that this can result in strong suppression of presentation of some T cell epitopes. This effect was observed when the antibody specificity was a B cell surface Ig, or formed part of an immune complex. In the latter case the presence of the suppressing antibody boosts presentation of other T cell epitopes through enhanced uptake into Fc receptor bearing cells. The influence of bound antibodies on the outcome of antigen processing may influence with T cell epitopes dominate T cell responses and may change the focus of the response with time.

Roles for asparagine endopeptidase in class II MHC-restricted antigen processing

2003 ◽  
Vol 70 ◽  
pp. 31-38 ◽  
Author(s):  
Colin Watts ◽  
Daniela Mazzeo ◽  
Michelle A. West ◽  
Stephen P. Matthews ◽  
Doreen Keane ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Adaptive Immune Response ◽  
Class Ii ◽  
Specific Class ◽  
T Cell Epitopes ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Few Data ◽  
Peptide Display

The adaptive immune response depends on the creation of suitable peptides from foreign antigens for display on MHC molecules to T lymphocytes. Similarly, MHC-restricted display of peptides derived from self proteins results in the elimination of many potentially autoreactive T cells. Different proteolytic systems are used to generate the peptides that are displayed as T cell epitopes on class I compared with class II MHC molecules. In the case of class II MHC molecules, the proteases that reside within the endosome/lysosome system of antigen-presenting cells are responsible; surprisingly, however, there are relatively few data on which enzymes are involved. Recently we have asked whether proteolysis is required simply in a generic sense, or whether the action of particular enzymes is needed to generate specific class II MHC-associated T cell epitopes. Using the recently identified mammalian asparagine endopeptidase as an example, we review recent evidence that individual enzymes can make clear and non-redundant contributions to MHC-restricted peptide display.

scholarly journals Presence and regulation of messenger ribonucleic acids encoding components of the class II major histocompatibility complex-associated antigen processing pathway in the bovine corpus luteum

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 689-698 ◽  
Author(s):  
Matthew J Cannon ◽  
John S Davis ◽  
Joy L Pate
Keyword(s):  
Corpus Luteum ◽  
Estrous Cycle ◽  
Antigen Processing ◽  
Class Ii ◽  
Luteal Cells ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Class Ii Mhc ◽  
Luteal Tissue ◽  
Antigen Presenting

Luteal cells express class II major histocompatibility complex (MHC) molecules and can stimulate T lymphocyte proliferationin vitro. However, it is unknown whether luteal cells express the intracellular components necessary to process the peptides presented by class II MHC molecules. The objective of the present study was to examine the expression and regulation of three major class II-associated antigen processing components – class II MHC-associated invariant chain (Ii), DMα and DMβ – in luteal tissue. Corpora lutea were collected early in the estrous cycle, during midcycle and late in the estrous cycle, and at various times following administration of a luteolytic dose of prostaglandin F2α(PGF2α) to the cow. Northern analysis revealed the presence of mRNA encoding each of the class II MHC-associated antigen processing proteins in luteal tissue. Ii mRNA concentrations did not change during the estrous cycle, whereas DMα and DMβ mRNA concentrations were highest in midcycle luteal tissue compared with either early or late luteal tissue. Tumor necrosis factor-α (TNF-α) reduced DMα mRNA concentrations in cultured luteal cells in the presence of LH or PGF2α. DMα and DMβ mRNA were also present in highly enriched cultures of luteal endothelial (CLENDO) cells, and DMα mRNA concentrations were greater in CLENDO cultures compared with mixed luteal cell cultures. Expression of invariant chain, DMα and DMβ genes indicates that cells within the corpus luteum express the minimal requirements to act as functional antigen-presenting cells, and the observation that CLENDO cells are a source of DMα and DMβ mRNA indicates that non-immune cells within the corpus luteum may function as antigen-presenting cells.

scholarly journals Endogenous viral antigen processing generates peptide-specific MHC class I cell-surface clusters

2012 ◽  
Vol 109 (38) ◽  
pp. 15407-15412 ◽  
Author(s):  
Xiuju Lu ◽  
James S. Gibbs ◽  
Heather D. Hickman ◽  
Alexandre David ◽  
Brian P. Dolan ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
Antigen Processing ◽  
Cell Receptor ◽  
Class I ◽  
Antigen Presenting Cell ◽  
Mhc Molecules ◽  
Specific Complex ◽  
Cognate Antigen ◽  
Antigen Presenting

Sensitivity is essential in CD8+ T-cell killing of virus-infected cells and tumor cells. Although the affinity of the T-cell receptor (TCR) for antigen is relatively low, the avidity of T cell-antigen–presenting cell interactions is greatly enhanced by increasing the valence of the interaction. It is known that TCRs cluster into protein islands after engaging their cognate antigen (peptides bound to MHC molecules). Here, we show that mouse Kb class I molecules segregate into preformed, long-lasting (hours) clusters on the antigen-presenting cell surface based on their bound viral peptide. Peptide-specific Kb clustering occurs when source antigens are expressed by vaccinia or vesicular stomatitis virus, either as proteasome-liberated precursors or free intracellular peptides. By contrast, Kb–peptide complexes generated by incubating cells with synthetic peptides are extensively intermingled on the cell surface. Peptide-specific complex sorting is first detected in the Golgi complex, and compromised by removing the Kb cytoplasmic tail. Peptide-specific clustering is associated with increased T-cell sensitivity: on a per-complex basis, endogenous SIINFEKL activates T cells more efficiently than synthetic SIINFEKL, and wild-type Kb presents endogenous SIINFEKL more efficiently than tailless Kb. We propose that endogenous processing generates peptide-specific clusters of class I molecules to maximize the sensitivity and speed of T-cell immunosurveillance.

scholarly journals Encapsulation of Cryptococcus neoformans with Glucuronoxylomannan Inhibits the Antigen-Presenting Capacity of Monocytes

1998 ◽  
Vol 66 (2) ◽  
pp. 664-669 ◽  
Author(s):  
Cinzia Retini ◽  
Anna Vecchiarelli ◽  
Claudia Monari ◽  
Francesco Bistoni ◽  
Thomas R. Kozel
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cryptococcus Neoformans ◽  
T Cell Responses ◽  
Class Ii ◽  
Mhc Molecules ◽  
Cell Responses ◽  
Class Ii Mhc ◽  
Antigen Presenting ◽  
Cells Cultured

ABSTRACT This report examines the effect of the major capsular polysaccharide of Cryptococcus neoformans, glucuronoxylomannan (GXM), on the antigen-presenting capability of human monocytes treated with acapsular cells of C. neoformans. We found that pretreatment of acapsular cryptococci with GXM downregulates, in a dose-dependent manner, the antigen-presenting capacity of monocytes, leading to reduced proliferative T-lymphocyte responses. Similar levels of suppression occurred when monocytes were exposed to encapsulated cryptococci or acapsular cryptococci that were pretreated with GXM. The magnitude of the T-cell response correlated with the ability of monocytes to ingest the yeast. Supernatant fluids from cocultures of monocytes and T cells cultured with encapsulated cryptococci contained higher levels of interleukin-10 (IL-10) than supernatant fluids of cells with acapsular cryptococci. Addition of anti-IL-10 monoclonal antibodies to the incubation medium of monocytes and T cells cultured with encapsulated cryptococci restored proliferative T-cell responses to levels observed during culture with acapsular cryptococci. Finally, treatment of monocytes with encapsulated cryptococci or GXM-treated acapsular cryptococci suppressed expression of class II major histocompatibility complex (MHC) molecules in a manner consistent with previous reports of IL-10-mediated suppression of class II MHC molecules and suppression of proliferative T-cell responses. These results suggest a link between GXM encapsulation, increased IL-10 synthesis by monocytes, decreased expression of class II MHC molecules on monocytes, and reduced proliferative T-cell responses.

scholarly journals Human TCR-MHC coevolution after divergence from mice includes increased nontemplate-encoded CDR3 diversity

2017 ◽  
Vol 214 (11) ◽  
pp. 3417-3433 ◽  
Author(s):  
Xiaojing Chen ◽  
Lucia Poncette ◽  
Thomas Blankenstein
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cell Receptor ◽  
Mhc Molecules ◽  
Mhc Ii ◽  
Cdr3 Length ◽  
Tcr Repertoire ◽  
Cell Diversity ◽  
Antigen Presenting

For thymic selection and responses to pathogens, T cells interact through their αβ T cell receptor (TCR) with peptide–major histocompatibility complex (MHC) molecules on antigen-presenting cells. How the diverse TCRs interact with a multitude of MHC molecules is unresolved. It is also unclear how humans generate larger TCR repertoires than mice do. We compared the TCR repertoire of CD4 T cells selected from a single mouse or human MHC class II (MHC II) in mice containing the human TCR gene loci. Human MHC II yielded greater thymic output and a more diverse TCR repertoire. The complementarity determining region 3 (CDR3) length adjusted for different inherent V-segment affinities to MHC II. Humans evolved with greater nontemplate-encoded CDR3 diversity than did mice. Our data, which demonstrate human TCR–MHC coevolution after divergence from rodents, explain the greater T cell diversity in humans and suggest a mechanism for ensuring that any V–J gene combination can be selected by a single MHC II.

scholarly journals Inherent reactivity of unselected TCR repertoires to peptide-MHC molecules

2019 ◽  
Vol 116 (44) ◽  
pp. 22252-22261 ◽  
Author(s):  
S. Harsha Krovi ◽  
John W. Kappler ◽  
Philippa Marrack ◽  
Laurent Gapin
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Selective Pressure ◽  
Dominant Role ◽  
Antigen Receptors ◽  
Complex Molecules ◽  
Peptide Antigens ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Antigen Presenting

The repertoire of αβ T cell antigen receptors (TCRs) on mature T cells is selected in the thymus where it is rendered both self-tolerant and restricted to the recognition of major histocompatibility complex molecules presenting peptide antigens (pMHC). It remains unclear whether germline TCR sequences exhibit an inherent bias to interact with pMHC prior to selection. Here, we isolated TCR libraries from unselected thymocytes and upon reexpression of these random TCR repertoires in recipient T cell hybridomas, interrogated their reactivities to antigen-presenting cell lines. While these random TCR combinations could potentially have reacted with any surface molecule on the cell lines, the hybridomas were stimulated most frequently by pMHC ligands. The nature and CDR3 loop composition of the TCRβ chain played a dominant role in determining pMHC-reactivity. Replacing the germline regions of mouse TCRβ chains with those of other jawed vertebrates preserved reactivity to mouse pMHC. Finally, introducing the CD4 coreceptor into the hybridomas increased the proportion of cells that could respond to pMHC ligands. Thus, αβ TCRs display an intrinsic and evolutionary conserved bias for pMHC molecules in the absence of any selective pressure, which is further strengthened in the presence of coreceptors.

scholarly journals Endogenous Presentation of CD8+ T Cell Epitopes from Epstein-Barr Virus–encoded Nuclear Antigen 1

2004 ◽  
Vol 199 (10) ◽  
pp. 1421-1431 ◽  
Author(s):  
Judy Tellam ◽  
Geoff Connolly ◽  
Katherine J. Green ◽  
John J. Miles ◽  
Denis J. Moss ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antigen Processing ◽  
Epstein Barr Virus ◽  
Cd8 T Cell ◽  
Nuclear Antigen ◽  
T Cell Epitopes ◽  
Barr Virus ◽  
Degradation Rates ◽  
Epstein Barr

Epstein-Barr virus (EBV)–encoded nuclear antigen (EBNA)1 is thought to escape cytotoxic T lymphocyte (CTL) recognition through either self-inhibition of synthesis or by blockade of proteasomal degradation by the glycine-alanine repeat (GAr) domain. Here we show that EBNA1 has a remarkably varied cell type–dependent stability. However, these different degradation rates do not correspond to the level of major histocompatibility complex class I–restricted presentation of EBNA1 epitopes. In spite of the highly stable expression of EBNA1 in B cells, CTL epitopes derived from this protein are efficiently processed and presented to CD8+ T cells. Furthermore, we show that EBV-infected B cells can readily activate EBNA1-specific memory T cell responses from healthy virus carriers. Functional assays revealed that processing of these EBNA1 epitopes is proteasome and transporter associated with antigen processing dependent. We also show that the endogenous presentation of these epitopes is dependent on the newly synthesized protein rather than the long-lived stable EBNA1. Based on these observations, we propose that defective ribosomal products, not the full-length antigen, are the primary source of endogenously processed CD8+ T cell epitopes from EBNA1.

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