home
***
CD-ROM
|
disk
|
FTP
|
other
***
search
/
The Arsenal Files 6
/
The Arsenal Files 6 (Arsenal Computer).ISO
/
health
/
med9603.zip
/
M9630683.TXT
< prev
next >
Wrap
Text File
|
1996-02-27
|
3KB
|
47 lines
Document 0683
DOCN M9630683
TI Sensitization of MHC class I-restricted T cells to exogenous proteins:
evidence for an alternative class I-restricted antigen presentation
pathway.
DT 9603
AU Martinez-Kinader B; Lipford GB; Wagner H; Heeg K; Institute for Medical
Microbiology and Hygiene, Technical; University of Munich, Germany.
SO Immunology. 1995 Oct;86(2):287-95. Unique Identifier : AIDSLINE
MED/96096250
AB Immunization with exogenous proteins usually fails to immunize CD8+ T
cells in vivo. Here we report that chicken ovalbumin (OVA) denatured by
heat or sodium dodecyl sulphate (SDS) effectively induced CD8+ cytolytic
T cells in vivo. The cytolytic T-lymphocyte (CTL) population generated
recognized syngeneic target cells pulsed with the immunodominant OVA
peptide (257-264) or transfected with the OVA protein-encoding gene. To
analyse the mechanisms of how denatured OVA enters the class
I-restricted pathway of antigen presentation, we took advantage of the
fact that denatured OVA sensitizes target cells in vitro for lysis by
OVA-specific CTL. We found that neither inhibition of protein synthesis
(by cycloheximide) nor blocking of transport via the Golgi apparatus (by
brefeldin A) interfered with the class I-restricted presentation of
denatured OVA in vitro. In addition, transporter associated with antigen
presentation (TAP)-dependent transport into the endoplasmic reticulum
(ER) was not required for effective presentation, as TAP-deficient cells
(RMA-S) could be sensitized effectively by denatured OVA for recognition
by class I-restricted CTL. In contrast, class I-restricted presentation
of denatured OVA was sensitive to lysosomotropic agents (NH4Cl,
vinblastine and leupeptin), indicating that endosomal-like compartments
are involved in the presentation of denatured OVA. Sensitization was
inhibited at low temperature, yet took place in the presence of sucrose
and in the absence of K+, indicating that denatured OVA enters the cell
via fluid-phase endocytosis. Hence the results provide further evidence
for an alternative class I-restricted pathway of antigen presentation
for exogenous proteins. As that pathway seems to be effective in vivo,
it offers a new and effective way of vaccination of CD8+ CTL.
DE Amino Acid Sequence Animal Antigen Presentation/*IMMUNOLOGY Cell
Culture CD8-Positive T-Lymphocytes/*IMMUNOLOGY Endocytosis/IMMUNOLOGY
Female Heat Histocompatibility Antigens Class I/*IMMUNOLOGY
Lysosomes/IMMUNOLOGY Mice Mice, Inbred C57BL Molecular Sequence Data
Ovalbumin/*IMMUNOLOGY Protein Denaturation Sodium Dodecyl Sulfate
Support, Non-U.S. Gov't JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).