Pleiotropic consequences of metabolic stress for the major histocompatibility complex class II molecule antigen processing and presentation machinery

Immunity ◽  
2021 ◽  
Author(s):  
Cristina C. Clement ◽  
Padma P. Nanaware ◽  
Takahiro Yamazaki ◽  
Maria Pia Negroni ◽  
Karthik Ramesh ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Antigen Processing ◽  
Metabolic Stress ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Antigen Processing And Presentation

scholarly journals Separation of subcellular compartments containing distinct functional forms of MHC class II.

1994 ◽  
Vol 125 (3) ◽  
pp. 595-605 ◽  
Author(s):  
Y Qiu ◽  
X Xu ◽  
A Wandinger-Ness ◽  
D P Dalke ◽  
S K Pierce
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Antigen Processing ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Subcellular Compartments ◽  
Early Endosomes ◽  
Dense Vesicles

Antigen processing in B lymphocytes entails initial binding of antigen to the surface Ig and internalization of the antigen into acidic compartments where the antigen is degraded, releasing peptides for binding to major histocompatibility complex class II molecules. Using subcellular fractionation techniques we show that functional, processed antigen-class II complexes capable of activating antigen-specific T cells in vitro are first formed in dense vesicles cosedimenting with lysosomes which are distinct from early endosomes and the bulk of late endosomes. With time, processed antigen-class II complexes appear in vesicles sedimenting with early endosomes and finally cofractionate with plasma membrane. A separate compartment is identified which contains major histocompatibility complex class II receptive to peptide binding but which does not have access to processed antigen in the B cell. These class II molecules are in the so-called "floppy" form in contrast to the class II molecules in the very dense vesicles which are in the "compact" form. These results demonstrate a correlation between the floppy and compact forms of class II molecules and their association with processed antigen and show that floppy and compact forms of class II reside in distinct and physically separable subcellular compartments.

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.

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