Roles for asparagine endopeptidase in class II MHC-restricted antigen processing

2003 ◽  
Vol 70 ◽  
pp. 31-38 ◽  
Author(s):  
Colin Watts ◽  
Daniela Mazzeo ◽  
Michelle A. West ◽  
Stephen P. Matthews ◽  
Doreen Keane ◽  
...  

The adaptive immune response depends on the creation of suitable peptides from foreign antigens for display on MHC molecules to T lymphocytes. Similarly, MHC-restricted display of peptides derived from self proteins results in the elimination of many potentially autoreactive T cells. Different proteolytic systems are used to generate the peptides that are displayed as T cell epitopes on class I compared with class II MHC molecules. In the case of class II MHC molecules, the proteases that reside within the endosome/lysosome system of antigen-presenting cells are responsible; surprisingly, however, there are relatively few data on which enzymes are involved. Recently we have asked whether proteolysis is required simply in a generic sense, or whether the action of particular enzymes is needed to generate specific class II MHC-associated T cell epitopes. Using the recently identified mammalian asparagine endopeptidase as an example, we review recent evidence that individual enzymes can make clear and non-redundant contributions to MHC-restricted peptide display.

1993 ◽  
Vol 178 (4) ◽  
pp. 1459-1463 ◽  
Author(s):  
C Watts ◽  
A Lanzavecchia

Immunoglobulins drive efficient antigen capture by antigen presenting cells for processing and presentation on class II MHC-molecules. High affinity antibody/antigen interactions are stable at endosomal/lysosomal pH thus altering the substrate for antigen processing. We show that this can result in strong suppression of presentation of some T cell epitopes. This effect was observed when the antibody specificity was a B cell surface Ig, or formed part of an immune complex. In the latter case the presence of the suppressing antibody boosts presentation of other T cell epitopes through enhanced uptake into Fc receptor bearing cells. The influence of bound antibodies on the outcome of antigen processing may influence with T cell epitopes dominate T cell responses and may change the focus of the response with time.


1986 ◽  
Vol 163 (5) ◽  
pp. 1314-1318 ◽  
Author(s):  
M Zauderer ◽  
A Iwamoto ◽  
T W Mak

gamma gene rearrangements similar to those described for cytotoxic T cell lines are found in L3T4+, autoreactive, or KLH-specific cloned helper T cell lines. High levels of gamma RNA transcripts were, in addition, detected in four out of five L3T4+, class II MHC-specific, autoreactive T cell clones, and in at least one of three KLH-specific, class II MHC-restricted clones. This contrasts with previously reported (9) expression of gamma RNA in only 1 of 11 antigen-specific helper T cell lines.


Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 689-698 ◽  
Author(s):  
Matthew J Cannon ◽  
John S Davis ◽  
Joy L Pate

Luteal cells express class II major histocompatibility complex (MHC) molecules and can stimulate T lymphocyte proliferationin vitro. However, it is unknown whether luteal cells express the intracellular components necessary to process the peptides presented by class II MHC molecules. The objective of the present study was to examine the expression and regulation of three major class II-associated antigen processing components – class II MHC-associated invariant chain (Ii), DMα and DMβ – in luteal tissue. Corpora lutea were collected early in the estrous cycle, during midcycle and late in the estrous cycle, and at various times following administration of a luteolytic dose of prostaglandin F2α(PGF2α) to the cow. Northern analysis revealed the presence of mRNA encoding each of the class II MHC-associated antigen processing proteins in luteal tissue. Ii mRNA concentrations did not change during the estrous cycle, whereas DMα and DMβ mRNA concentrations were highest in midcycle luteal tissue compared with either early or late luteal tissue. Tumor necrosis factor-α (TNF-α) reduced DMα mRNA concentrations in cultured luteal cells in the presence of LH or PGF2α. DMα and DMβ mRNA were also present in highly enriched cultures of luteal endothelial (CLENDO) cells, and DMα mRNA concentrations were greater in CLENDO cultures compared with mixed luteal cell cultures. Expression of invariant chain, DMα and DMβ genes indicates that cells within the corpus luteum express the minimal requirements to act as functional antigen-presenting cells, and the observation that CLENDO cells are a source of DMα and DMβ mRNA indicates that non-immune cells within the corpus luteum may function as antigen-presenting cells.


1989 ◽  
Vol 170 (1) ◽  
pp. 279-289 ◽  
Author(s):  
D L Perkins ◽  
M Z Lai ◽  
J A Smith ◽  
M L Gefter

Previous data from many groups show that both class I and class II-restricted T cells recognize short synthetic peptides in the context of their respective MHC molecules (9-18), all of the peptides described to date are restricted to only a single class of MHC molecules; however, structural homology between the class I and II MHC molecules and the use of similar TCRs by class I and II-restricted T cells suggest that antigen recognition mechanisms are similar in both systems. To directly compare antigen recognition in the two systems, we analyzed peptides for the ability to function in both a class I and II-restricted system and found that seven of seven individual peptides tested stimulate both class I and II-restricted T cell responses. In addition, two of the peptides can function in different species stimulating both human class I and murine class II T cell responses. Thus, the process of T cell recognition of antigen in the context of MHC molecules was highly conserved in evolution not only between the class I and class II MHC systems, but also between the murine and human species.


Hybridoma ◽  
1989 ◽  
Vol 8 (3) ◽  
pp. 263-275 ◽  
Author(s):  
ESTEBAN CELIS ◽  
DAWEI OU ◽  
BERNHARD DIETZSCHOLD ◽  
LASZLO OTVOS ◽  
HILARY KOPROWSKI

Vaccine ◽  
1995 ◽  
Vol 13 (2) ◽  
pp. 142-150 ◽  
Author(s):  
Naresh K. Verma ◽  
H. Kirk Ziegler ◽  
Michael Wilson ◽  
Maqsood Khan ◽  
Susan Safley ◽  
...  

1989 ◽  
Vol 170 (6) ◽  
pp. 1879-1886 ◽  
Author(s):  
P von Hoegen ◽  
M C Miceli ◽  
B Tourvieille ◽  
M Schilham ◽  
J R Parnes

We have examined the ability of hCD4 to interact functionally with mouse class II MHC molecules using the mouse T cell hybridoma BI-141, specific for beef insulin. We have previously shown that expression of mouse CD4 results in a marked enhancement of IL-2 release by BI-141 cells in response to beef insulin or, in a cross-reactive response, to pork insulin, on the appropriate mouse APCs. We now demonstrate that expression of hCD4 results in an equivalent stimulation of antigen responses by this mouse T cell hybridoma. The specificity of this effect was demonstrated by mAb and gp120 blocking studies. These data provide the first direct evidence for function of hCD4 and in an exclusively mouse system.


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