scholarly journals Reduction of disulfide bonds during antigen processing: evidence from a thiol-dependent insulin determinant.

1991 ◽  
Vol 174 (5) ◽  
pp. 1121-1130 ◽  
Author(s):  
P E Jensen
Keyword(s):  
T Cells ◽  
Disulfide Bonds ◽  
Antigen Processing ◽  
Strong Support ◽  
Class Ii ◽  
Protein Antigens ◽  
Competition Binding ◽  
Peptide Binding Site ◽  
A Chain ◽  
Necessary And Sufficient

Previous studies have demonstrated that insulin, like other protein antigens, requires processing in metabolically active antigen-presenting cells (APC) before it can be recognized by class II-restricted T lymphocytes. Unlike many other proteins, insulin peptides of minimal size retain the requirement for antigen processing. We demonstrate that this requirement can be bypassed by incubation of insulin with reducing agents in the presence of aldehyde-fixed APC. Fixed APC treated in this way were able to stimulate I-Ab- and I-Ad-restricted T cell hybridomas. Data are presented that demonstrate that cloned and polyclonal T cells recognize a determinant within the NH2-terminal 14 residues of the beef insulin A chain with no requirement for B chain residues. The common feature among peptides capable of stimulating these cells in the presence of live APC is the chemical form of the cysteine thiol groups. Those forms that produce free thiols upon reduction are active, whereas those with irreversibly protected sulfhydryls are not. Functional experiments with fixed APC and competition binding experiments with purified I-Ad indicate that only A chain peptides with free thiols are able to stably associate with the peptide-binding site on class II in a form that is recognized by specific T cells. Our findings indicate that reduction of disulfide bonds is both necessary and sufficient for presentation of insulin to a major population of class II-restricted T cells. The results provide strong support for the hypothesis that protein disulfides can be reduced during physiologic antigen processing.

scholarly journals Major histocompatibility complex class II-associated peptides control the presentation of bacterial superantigens to T cells.

1996 ◽  
Vol 183 (3) ◽  
pp. 1083-1092 ◽  
Author(s):  
R Wen ◽  
G A Cole ◽  
S Surman ◽  
M A Blackman ◽  
D L Woodland
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Antigen Processing ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Bacterial Superantigens ◽  
Toxic Shock Syndrome Toxin

Recent studies have shown that only a subset of major histocompatibility complex (MHC) class II molecules are able to present bacterial superantigens to T cells, leading to the suggestion that class-II associated peptides may influence superantigen presentation. Here, we have assessed the potential role of peptides on superantigen presentation by (a) analyzing the ability of superantigens to block peptide-specific T cell responses and (b) analyzing the ability of individual peptides to promote superantigen presentation on I-Ab-expressing T2 cells that have a quantitative defect in antigen processing. A series of peptides is described that specifically promote either toxic shock syndrome toxin (TSST) 1 or staphylococcal enterotoxin A (SEA) presentation. Whereas some peptides promoted the presentation of TSST-1 (almost 5,000-fold in the case of one peptide), other peptides promoted the presentation of SEA. These data demonstrate that MHC class II-associated peptides differentially influence the presentation of bacterial superantigens to T cells.

scholarly journals Functional comparison of spleen dendritic cells and dendritic cells cultured in vitro from bone marrow precursors

Blood ◽  
1996 ◽  
Vol 88 (9) ◽  
pp. 3508-3512 ◽  
Author(s):  
K Garrigan ◽  
P Moroni-Rawson ◽  
C McMurray ◽  
I Hermans ◽  
N Abernethy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Antigen Processing ◽  
Class Ii ◽  
Protein Antigen ◽  
Soluble Antigen

We have compared dendritic cells (DC) isolated from mouse spleen, or generated in vitro from bone marrow (BM) precursors cultured in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), for the ability to process and present soluble antigen and stimulate major histocompatibility complex (MHC) Class II-restricted T cells. DC from spleen or BM cultures were equally able to stimulate the in vitro proliferation of allogeneic T cells or of antigen-specific T-cell receptor (TCR)-transgenic T cells. Both DC populations also induced comparable levels of IL-2 secretion by a T-cell hybridoma. Therefore, splenic and BM-derived DC express comparable levels of (Antigen + MHC Class II) ligands and/or costimulatory molecules and have comparable ability to stimulate T-cell responses. When presentation of a native protein antigen, rather than peptide, was evaluated, BM-derived DC were at least 50 times better than splenic DC at stimulating the proliferation of TCR-transgenic T cells. The antigen processing ability of the two populations was similar only when splenic DC were used immediately ex vivo. Therefore, unlike spleen DC, BM-derived DC maintain the capacity to process protein antigen for MHC Class II presentation during in vitro culture. Due to these characteristics, BM-derived DC may represent a useful tool in immunotherapy studies, as they combine high T-cell stimulatory properties with the capacity to process and present native antigen.

scholarly journals A step-by-step overview of the dynamic process of epitope selection by major histocompatibility complex class II for presentation to helper T cells

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1305 ◽  
Author(s):  
Scheherazade Sadegh-Nasseri
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Antigen Processing ◽  
Class Ii ◽  
Helper T Cells ◽  
Target Antigen ◽  
Major Histocompatibility ◽  
Antigen Receptors ◽  
Histocompatibility Complex ◽  
Epitope Selection

T cell antigen receptors (TCRs) expressed on cytotoxic or helper T cells can only see their specific target antigen as short sequences of peptides bound to the groove of proteins of major histocompatibility complex (MHC) class I, and class II respectively. In addition to the many steps, several participating proteins, and multiple cellular compartments involved in the processing of antigens, the MHC structure, with its dynamic and flexible groove, has perfectly evolved as the underlying instrument for epitope selection. In this review, I have taken a step-by-step, and rather historical, view to describe antigen processing and determinant selection, as we understand it today, all based on decades of intense research by hundreds of laboratories.

scholarly journals Mycobacterium tuberculosis Promotes HIV trans-Infection and Suppresses Major Histocompatibility Complex Class II Antigen Processing by Dendritic Cells

2010 ◽  
Vol 84 (17) ◽  
pp. 8549-8560 ◽  
Author(s):  
Morgan A. Reuter ◽  
Nicole D. Pecora ◽  
Clifford V. Harding ◽  
David H. Canaday ◽  
David McDonald
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Cd4 T Cells ◽  
Antigen Processing ◽  
Class Ii ◽  
Sub Saharan Africa ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

ABSTRACT Mycobacterium tuberculosis is a leading killer of HIV-infected individuals worldwide, particularly in sub-Saharan Africa, where it is responsible for up to 50% of HIV-related deaths. Infection by HIV predisposes individuals to M. tuberculosis infection, and coinfection accelerates the progression of both diseases. In contrast to most other opportunistic infections associated with HIV, an increased risk of M. tuberculosis infection occurs during early-stage HIV disease, long before CD4 T cell counts fall below critical levels. We hypothesized that M. tuberculosis infection contributes to HIV pathogenesis by interfering with dendritic cell (DC)-mediated immune control. DCs carry pathogens like M. tuberculosis and HIV from sites of infection into lymphoid tissues, where they process and present antigenic peptides to CD4 T cells. Paradoxically, DCs can also deliver infectious HIV to T cells without first becoming infected, a process known as trans-infection. Lipopolysaccharide (LPS)-activated DCs sequester HIV in pocketlike membrane invaginations that remain open to the cell surface, and individual virions are delivered from the pocket into T cells at the site of contact during trans-infection. Here we report that M. tuberculosis exposure increases HIV trans-infection and induces viral sequestration within surface-accessible compartments identical to those seen in LPS-stimulated DCs. At the same time, M. tuberculosis dramatically decreases the degradative processing and major histocompatibility complex class II (MHC-II) presentation of HIV antigens to CD4 T cells. Our data suggest that M. tuberculosis infection promotes a shift in the dynamic balance between antigen processing and intact virion presentation, favoring DC-mediated amplification of HIV infections.

scholarly journals Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity

2018 ◽  
Vol 215 (10) ◽  
pp. 2617-2635 ◽  
Author(s):  
Yoshinaga Ito ◽  
Orr Ashenberg ◽  
Jason Pyrdol ◽  
Adrienne M. Luoma ◽  
Orit Rozenblatt-Rosen ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Mhc Class Ii ◽  
Antigen Processing ◽  
Class Ii ◽  
Single Amino Acid ◽  
Invariant Chain ◽  
Presentation Pathway ◽  
Single Amino Acid Change

A number of autoimmunity-associated MHC class II proteins interact only weakly with the invariant chain–derived class II–associated invariant chain peptide (CLIP). CLIP dissociates rapidly from I-Ag7 even in the absence of DM, and this property is related to the type 1 diabetes–associated β57 polymorphism. We generated knock-in non-obese diabetic (NOD) mice with a single amino acid change in the CLIP segment of the invariant chain in order to moderately slow CLIP dissociation from I-Ag7. These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within β cell secretory granules. Rapid CLIP dissociation enhanced the presentation of such extracellular peptides, thus bypassing the conventional MHC class II antigen-processing pathway. Autoimmunity-associated MHC class II polymorphisms therefore not only modify binding of self-peptides, but also alter the biochemistry of peptide acquisition.

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