scholarly journals Regulation of antigen presentation by acidic pH.

1990 ◽  
Vol 171 (5) ◽  
pp. 1779-1784 ◽  
Author(s):  
P E Jensen
Keyword(s):  
T Cells ◽  
Complex Formation ◽  
Ph Dependence ◽  
Peptide Binding ◽  
Class Ii ◽  
Acidic Ph ◽  
Peptide Antigens ◽  
General Importance ◽  
Class Ii Mhc ◽  
Functional Peptide

The effect of pH on functional association of peptide antigens with APC membranes was investigated by using aldehyde-fixed B cells and class II-restricted T cell hybridomas to assess antigen/MHC complex formation. The results indicated that the rate and extent of functional peptide binding was markedly increased at pH 5.0 as compared with pH 7.3. The pH dependence of binding was preserved after pretreatment of fixed APC with pH 5.0 buffer, suggesting that pH had a direct effect on the interaction of peptide with the APC membrane. Similar results were obtained by using several peptides and I-Ad- and I-Ed-restricted T cells, indicating that pH may be of general importance in regulating the formation of functional antigen/class II MHC complexes.

scholarly journals Class II MHC molecules are present in macrophage lysosomes and phagolysosomes that function in the phagocytic processing of Listeria monocytogenes for presentation to T cells.

1992 ◽  
Vol 119 (3) ◽  
pp. 531-542 ◽  
Author(s):  
C V Harding ◽  
H J Geuze
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
Class Ii ◽  
Peritoneal Macrophages ◽  
Peptide Antigens ◽  
Mhc Molecules ◽  
Immunogenic Peptides ◽  
Class Ii Mhc ◽  
Bacterial Antigens ◽  
Mannose 6 Phosphate

Phagocytic processing of heat-killed Listeria monocytogenes by peritoneal macrophages resulted in degradation of these bacteria in phagolysosomal compartments and processing of bacterial antigens for presentation to T cells by class II MHC molecules. Within 20 min of uptake by macrophages, Listeria peptide antigens were expressed on surface class II MHC molecules, capable of stimulating Listeria-specific T cells. Within this period, degradation of labeled bacteria to acid-soluble low molecular weight catabolites also commenced. Immunoelectron microscopy was used to evaluate the compartments involved in this processing. Upon uptake of the bacteria, phagosomes containing Listeria fused rapidly with both lysosomes and endosomes. Class II MHC molecules were present in a tubulo-vesicular lysosome compartment, which appeared to fuse with phagosomes, as well as in the resulting phagolysosomes containing internalized Listeria; these compartments were all positive for Lamp 1 and cathepsin D and lacked 46-kD mannose-6-phosphate receptors. In addition, class II MHC and Lamp 1 were co-localized in vesicles of the trans Golgi reticulum, where they were segregated from 46-kD mannose-6-phosphate receptors. Vesicles containing both Listeria-derived components and class II MHC molecules were also observed; some of these may represent vesicles recycling from phagolysosomes, potentially bearing processed immunogenic peptides complexed with class II MHC. These results support a central role for lysosomes and phagolysosomes in the processing of bacterial antigens for presentation to T cells. Tubulo-vesicular lysosomes appear to represent an important convergence of endocytic, phagocytic and biosynthetic pathways, where antigens may be processed to allow binding to class II MHC molecules and recycling to the cell surface.

scholarly journals Enhanced binding of peptide antigen to purified class II major histocompatibility glycoproteins at acidic pH.

1991 ◽  
Vol 174 (5) ◽  
pp. 1111-1120 ◽  
Author(s):  
P E Jensen
Keyword(s):  
Electrostatic Interactions ◽  
Antigen Processing ◽  
Ph Dependence ◽  
Peptide Binding ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Hydrogen Ion Concentration ◽  
Peptide Antigens ◽  
Antigen Presenting

Helper T lymphocytes recognize peptide antigens stably associated with class II major histocompatibility complex (MHC) glycoproteins on the surface of antigen-presenting cells and serve to regulate a wide variety of immune responses. A previous study from our laboratory had demonstrated that the functional association of various peptide antigens with the antigen-presenting cell membrane was increased at pH 5 as compared to pH 7, consistent with the potential role of acidic endosomal compartments in antigen processing. The mechanism for this effect was not determined. In the present study, assays using purified class II glycoprotein were used to further define this mechanism. The potential requirement for pH-dependent interactions involving non-MHC membrane components was excluded in functional assays with purified class II reconstituted in artificial membranes containing only neutral phospholipids and cholesterol. The association of HEL(104-120) with I-Ed, and OVA(323-339) with I-Ad, was increased at pH 5, as measured by activation of specific T cell hybridomas. An enzyme immunoassay was developed to measure the binding of biotin-labeled peptides to purified class II in detergent micelles. The pH dependence of binding paralleled our previous functional results. Optimum binding of biotin-HEL(104-120) to I-Ed was observed at pH approximately 4.5, whereas maximum binding of biotin-Myo(106-118) to I-Ad occurred at pH approximately 5.5. The latter peptide also bound weakly to I-Ed, but with a pH dependence similar to that observed using HEL(104-120). Further experiments with biotin-HEL(104-120)/I-Ed indicated that both the apparent affinity and the apparent concentration of peptide-binding sites are increased as hydrogen ion concentration is increased from pH 7 to pH 5. The effect of pH in this range was largely reversible and was not associated with a change in peptide dissociation that could be measured with our assay system. Binding was not inhibited in the presence of 1.5 M NaCl, suggesting that electrostatic interactions between HEL(104-120) and I-Ed are not essential for binding. It is proposed that protonation of a critical group(s) in the class II molecule regulates its capacity to form stable complexes with peptide. However, this effect alone does not fully account for the rapid kinetics of peptide binding observed in experiments with intact antigen-presenting cells.

scholarly journals Liver Damage Preferentially Results from CD8+ T Cells Triggered by High Affinity Peptide Antigens

1998 ◽  
Vol 188 (6) ◽  
pp. 1147-1157 ◽  
Author(s):  
Jennifer Q. Russell ◽  
Gregory J. Morrissette ◽  
Mark Weidner ◽  
Chirag Vyas ◽  
Deborah Aleman-Hoey ◽  
...  
Keyword(s):  
T Cells ◽  
Class Ii ◽  
Cd8 Cells ◽  
Peptide Antigens ◽  
High Affinity ◽  
Class Ii Mhc ◽  
Activated T Lymphocytes ◽  
Hepatocyte Damage ◽  
Affinity Peptide

Little is understood of the anatomical fate of activated T lymphocytes and the consequences they have on the tissues into which they migrate. Previous work has suggested that damaged lymphocytes migrate to the liver. This study compares class I versus class II major histocompatibility complex (MHC)–restricted ovalbumin-specific T cell antigen receptor (TCR) transgenic mice to demonstrate that after in vivo activation with antigen the emergence of CD4−CD8−B220+ T cells occurs more frequently from a CD8+ precursor than from CD4+ T cells. Furthermore, this change in phenotype is conferred only by the high affinity native peptide antigen and not by lower affinity peptide variants. After activation of CD8+ cells with only the high affinity peptide, there is also a dramatically increased number of liver lymphocytes with accompanying extensive hepatocyte damage and elevation of serum aspartate transaminase. This was not observed in mice bearing a class II MHC–restricted TCR. The findings show that CD4−CD8−B220+ T cells preferentially derive from a CD8+ precursor after a high intensity TCR signal. After activation, T cells can migrate to the liver and induce hepatocyte damage, and thereby serve as a model of autoimmune hepatitis.

MHC Sınıf I ve MHC Sınıf II Gen Düzenlenmesi

2020 ◽  
Vol 8 (3) ◽  
pp. 144-156
Author(s):  
Şule KARATAŞ ◽  
Fatma SAVRAN OĞUZ
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Gene Regulation ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Regulation Mechanisms

Introduction: Peptides obtained by processing intracellular and extracellular antigens are presented to T cells to stimulate the immune response. This presentation is made by peptide receptors called major histocompatibility complex (MHC) molecules. The regulation mechanisms of MHC molecules, which have similar roles in the immune response, especially at the gene level, have significant differences according to their class. Objective: Class I and class II MHC molecules encoded by MHC genes on the short arm of the sixth chromosome are peptide receptors that stimulate T cell response. These peptides, which will enable the recognition of the antigen from which they originate, are loaded into MHC molecules and presented to T cells. Although the principles of loading and delivering peptides are similar for both molecules, the peptide sources and peptide loading mechanisms are different. In addition, class I molecules are expressed in all nucleated cells while class II molecules are expressed only in Antigen Presentation Cells (APC). These differences; It shows that MHC class I is not expressed by exactly the same transcriptional mechanisms as MHC class II. In our article, we aimed to compare the gene expressions of both classes and reveal their similarities and differences. Discussion and Conclusion: A better understanding of the transcriptional mechanisms of MHC molecules will reveal the role of these molecules in diseases more clearly. In our review, we discussed MHC gene regulation mechanisms with presence of existing informations, which is specific to the MHC class, for contribute to future research. Keywords: MHC class I, MHC class II, MHC gene regulation, promoter, SXY module, transcription

scholarly journals Citrullination only infrequently impacts peptide binding to HLA class II MHC

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0177140 ◽  
Author(s):  
John Sidney ◽  
Stephane Becart ◽  
Mimi Zhou ◽  
Karen Duffy ◽  
Mikaela Lindvall ◽  
...  
Keyword(s):  
Peptide Binding ◽  
Class Ii ◽  
Hla Class Ii ◽  
Class Ii Mhc

scholarly journals Major histocompatibility complex-restricted recognition of retroviral superantigens by V beta 17+ T cells.

1992 ◽  
Vol 176 (1) ◽  
pp. 275-280 ◽  
Author(s):  
M A Blackman ◽  
F E Lund ◽  
S Surman ◽  
R B Corley ◽  
D L Woodland
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Direct Role ◽  
Histocompatibility Complex ◽  
Class Ii Mhc ◽  
Mhc Class Ii Molecules

It has been established that at least some V beta 17+ T cells interact with an endogenous superantigen encoded by the murine retrovirus, Mtv-9. To analyze the role of major histocompatibility complex (MHC) class II molecules in presenting the Mtv-9 encoded superantigen, vSAG-9 to V beta 17+ hybridomas, a panel of nine hybridomas was tested for their ability to respond to A20/2J (H-2d) and LBK (H-2a) cells which had been transfected with the vSAG-9 gene. Whereas some of the hybridomas recognized vSAG-9 exclusively in the context of H-2a, other hybridomas recognized vSAG-9 exclusively in the context of H-2d or in the context of both H-2d and H-2a. These results suggest that: (a) the class II MHC molecule plays a direct role in the recognition of retroviral superantigen by T cells, rather than serving simply as a platform for presentation; and, (b) it is likely that components of the TCR other than V beta are involved in the vSAG-9/TCR/class II interaction.

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