scholarly journals The many roads to cross-presentation

2005 ◽  
Vol 202 (10) ◽  
pp. 1313-1318 ◽  
Author(s):  
Tom A.M. Groothuis ◽  
Jacques Neefjes
Keyword(s):  
Endoplasmic Reticulum ◽  
T Lymphocytes ◽  
Mhc Class I ◽  
Cytotoxic T Lymphocytes ◽  
Class I ◽  
Cross Presentation ◽  
Peptide Loading ◽  
The Many ◽  
Mhc Class I Molecules

Cross-presentation of extracellular antigens by MHC class I molecules is required for priming cytotoxic T lymphocytes (CTLs) at locations remote from the site of infection. Various mechanisms have been proposed to explain cross-presentation. One such mechanism involves the fusion of the endoplasmic reticulum (ER) with the endosomal-phagosomal system, in which the machinery required for peptide loading of MHC class I molecules is introduced directly into the phagosome. Here, we discuss the evidence for and against the ER-phagosome concept as well as other possible mechanisms of cross-presentation.

scholarly journals Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells

1999 ◽  
Vol 190 (9) ◽  
pp. 1227-1240 ◽  
Author(s):  
Grégoire Lauvau ◽  
Kazuhiro Kakimi ◽  
Gabriele Niedermann ◽  
Marina Ostankovitch ◽  
Patricia Yotnda ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
T Lymphocytes ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Cytotoxic T Lymphocytes ◽  
Antigen Processing ◽  
High Efficiency ◽  
Class I ◽  
Aminopeptidase Activity

Antigen presentation by major histocompatibility complex (MHC) class I molecules requires peptide supply by the transporters associated with antigen processing (TAPs), which select substrates in a species- and, in the rat, allele-specific manner. Conflicts between TAPs and MHC preferences for COOH-terminal peptide residues in rodent cells strongly reduce the efficiency of MHC class I antigen presentation. Although human TAP is relatively permissive, some peptide ligands for human histocompatibility leukocyte antigen class I molecules are known to possess very low TAP affinities; the significance of these in vitro findings for cellular antigen presentation is not known. We studied two naturally immunodominant viral epitopes presented by HLA-A2 that display very low affinities for human TAP. Low TAP affinities preclude minimal epitope access to the endoplasmic reticulum (ER) and assembly with HLA-A2 in vitro, as well as presentation by minigene-expressing cells to cytotoxic T lymphocytes. However, NH2-terminally but not COOH-terminally extended epitope variants with higher TAP affinities assemble in vitro and are presented to cytotoxic T lymphocytes with high efficiency. Thus, human TAP can influence epitope selection and restrict access to the ER to epitope precursors. Analysis of TAP affinities of a panel of viral epitopes suggests that TAP selection of precursors may be a common phenomenon for HLA-A2–presented epitopes. We also analyzed HLA-A2–eluted peptides from minigene-expressing cells and show that an NH2-terminally extended variant with low A2 binding affinity undergoes ER processing, whereas another with high affinity is presented unmodified. Therefore, the previously reported aminopeptidase activity in the ER can also act on TAP-translocated peptides.

scholarly journals Redox-regulated Export of the Major Histocompatibility Complex Class I-Peptide Complexes from the Endoplasmic Reticulum

2009 ◽  
Vol 20 (14) ◽  
pp. 3285-3294 ◽  
Author(s):  
Sungwook Lee ◽  
Boyoun Park ◽  
Kwonyoon Kang ◽  
Kwangseog Ahn
Keyword(s):  
Endoplasmic Reticulum ◽  
Mhc Class I ◽  
Bound State ◽  
Class I ◽  
Histocompatibility Complex ◽  
Er Retention ◽  
Peptide Loading ◽  
Peptide Complexes ◽  
Protein Disulfide ◽  
Mhc Class I Molecules

In contrast to the fairly well-characterized mechanism of assembly of MHC class I-peptide complexes, the disassembly mechanism by which peptide-loaded MHC class I molecules are released from the peptide-loading complex and exit the endoplasmic reticulum (ER) is poorly understood. Optimal peptide binding by MHC class I molecules is assumed to be sufficient for triggering exit of peptide-filled MHC class I molecules from the ER. We now show that protein disulfide isomerase (PDI) controls MHC class I disassembly by regulating dissociation of the tapasin-ERp57 disulfide conjugate. PDI acts as a peptide-dependent molecular switch; in the peptide-bound state, it binds to tapasin and ERp57 and induces dissociation of the tapasin-ERp57 conjugate. In the peptide-free state, PDI is incompetent to bind to tapasin or ERp57 and fails to dissociate the tapasin-ERp57 conjugates, resulting in ER retention of MHC class I molecules. Thus, our results indicate that even after optimal peptide loading, MHC class I disassembly does not occur by default but, rather, is a regulated process involving PDI-mediated interactions within the peptide-loading complex.

scholarly journals Detection of major histocompatibility complex class I-restricted, HIV- specific cytotoxic T lymphocytes in the blood of infected hemophiliacs

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1909-1914 ◽  
Author(s):  
RA Koup ◽  
JL Sullivan ◽  
PH Levine ◽  
D Brettler ◽  
A Mahr ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Mhc Class I ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Class I ◽  
Gene Products ◽  
Major Histocompatibility ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

Abstract Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response.

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