Faculty Opinions recommendation of The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen-processing defects.

Author(s):  
Nilabh Shastri
2010 ◽  
Vol 207 (3) ◽  
pp. 671-671
Author(s):  
Cláudia C. Oliveira ◽  
Peter A. van Veelen ◽  
Bianca Querido ◽  
Arnoud de Ru ◽  
Marjolein Sluijter ◽  
...  

2004 ◽  
Vol 199 (10) ◽  
pp. 1421-1431 ◽  
Author(s):  
Judy Tellam ◽  
Geoff Connolly ◽  
Katherine J. Green ◽  
John J. Miles ◽  
Denis J. Moss ◽  
...  

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.


2017 ◽  
Author(s):  
Natalie J. Neubert ◽  
Laure Tillé ◽  
David Barras ◽  
Charlotte Soneson ◽  
Petra Baumgaertner ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3713-3722 ◽  
Author(s):  
Juliette Mouriès ◽  
Gabriel Moron ◽  
Géraldine Schlecht ◽  
Nicolas Escriou ◽  
Gilles Dadaglio ◽  
...  

Abstract Cross-presentation is a crucial mechanism in tumoral and microbial immunity because it allows internalized cell associated or exogenous antigens (Ags) to be delivered into the major histocompatibility complex I pathway. This pathway is important for the development of CD8+ T-cell responses and for the induction of tolerance. In mice, cross-presentation is considered to be a unique property of CD8α+ conventional dendritic cells (DCs). Here we show that splenic plasmacytoid DCs (pDCs) efficiently capture exogenous Ags in vivo but are not able to cross-present these Ags at steady state. However, in vitro and in vivo stimulation by Toll-like receptor-7, or -9 or viruses licenses pDCs to cross-present soluble or particulate Ags by a transporter associated with antigen processing-dependent mechanism. Induction of cross-presentation confers to pDCs the ability to generate efficient effector CD8+ T-cell responses against exogenous Ags in vivo, showing that pDCs may play a crucial role in induction of adaptive immune responses against pathogens that do not infect tissues of hemopoietic origin. This study provides the first evidence for an in vivo role of splenic pDCs in Ag cross-presentation and T-cell cross-priming and suggests that pDCs may constitute an attractive target to boost the efficacy of vaccines based on cytotoxic T lymphocyte induction.


2004 ◽  
Vol 78 (13) ◽  
pp. 7069-7078 ◽  
Author(s):  
Todd M. Allen ◽  
Marcus Altfeld ◽  
Xu G. Yu ◽  
Kristin M. O'Sullivan ◽  
Mathias Lichterfeld ◽  
...  

ABSTRACT Numerous studies now support that human immunodeficiency virus type 1 (HIV-1) evolution is influenced by immune selection pressure, with population studies showing an association between specific HLA alleles and mutations within defined cytotoxic T-lymphocyte epitopes. Here we combine sequence data and functional studies of CD8 T-cell responses to demonstrate that allele-specific immune pressures also select for mutations flanking CD8 epitopes that impair antigen processing. In persons expressing HLA-A3, we demonstrate consistent selection for a mutation in a C-terminal flanking residue of the normally immunodominant Gag KK9 epitope that prevents its processing and presentation, resulting in a rapid decline in the CD8 T-cell response. This single amino acid substitution also lies within a second HLA-A3-restricted epitope, with the mutation directly impairing recognition by CD8 T cells. Transmission of the mutation to subjects expressing HLA-A3 was shown to prevent the induction of normally immunodominant acute-phase responses to both epitopes. However, subsequent in vivo reversion of the mutation was coincident with delayed induction of new CD8 T-cell responses to both epitopes. These data demonstrate that mutations within the flanking region of an HIV-1 epitope can impair recognition by an established CD8 T-cell response and that transmission of these mutations alters the acute-phase CD8+ T-cell response. Moreover, reversion of these mutations in the absence of the original immune pressure reveals the potential plasticity of immunologically selected evolutionary changes.


2022 ◽  
Author(s):  
Tresa Rani Sarraf ◽  
Malini Sen

Antigen processing, cross-presentation, and antigen-specific CD8 T cell response form part and parcel of T cell-mediated immunity. Yet, lacunae remain in our understanding of antigen processing/presentation and CD8 T cell response. Given the association of Wnt5A signaling with immune homeostasis, we evaluated the utility of Wnt5A in antigen processing, cross-presentation, and CD8 T cell activation. Using mouse bone marrow-derived dendritic cells as antigen-presenting cells and ovalbumin as a model antigen we found that Wnt5A mediated regulation of actin and proteasome dynamics is inherently associated with antigen processing. A Wnt5A-Actin-Protasome axis also contributes to antigen cross-presentation and antigen responsive CD8 T cell expansion. In concurrence with these observations, we demonstrated impaired activation of ovalbumin-specific CD8 T cells in ovalbumin immunized Wnt5A heterozygous mice as illustrated by their poor CD8 T cell recall response to ovalbumin when compared to similarly immunized wild type cohorts. Our results suggest that Wnt5A signaling-directed antigen processing/presentation could be vital for generating CD8 T cell recall response to antigen, thus shedding light on a critical parameter of immunity.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 98 ◽  
Author(s):  
Derek Theisen ◽  
Kenneth Murphy

The cDC1 subset of classical dendritic cells is specialized for priming CD8 T cell responses through the process of cross-presentation. The molecular mechanisms of cross-presentation remain incompletely understood because of limited biochemical analysis of rare cDC1 cells, difficulty in their genetic manipulation, and reliance onin vitrosystems based on monocyte- and bone-marrow-derived dendritic cells. This review will discuss cross-presentation from the perspective of studies with monocyte- or bone-marrow-derived dendritic cells while highlighting the need for future work examining cDC1 cells. We then discuss the role of cDC1s as a cellular platform to combine antigen processing for class I and class II MHC presentation to allow the integration of “help” from CD4 T cells during priming of CD8 T cell responses.


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