TY - JOUR
T1 - Antigen processing in vivo and the elicitation of primary CTL responses
AU - Restifo, Nicholas P.
AU - Bačík, Igor
AU - Irvine, Kari R.
AU - Yewdell, Jonathan W.
AU - McCabe, Barbra J.
AU - Anderson, Robert W.
AU - Eisenlohr, Laurence C.
AU - Rosenberg, Steven A.
AU - Bennink, Jack R.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1995
Y1 - 1995
N2 - CD8+ T lymphocytes (T(CD8+)) play an important role in cellular immune responses. T(CD8+) recognize MHC class I molecules complexed to peptides of 8 to 10 residues derived largely from cytosolic proteins. Proteins are generally thought to be fragmented in the cytoplasm and delivered to nascent class I molecules in the endoplasmic reticulum (ER) by a peptide transporter encoded by the MHC. To explore the extent to which T(CD8+) induction in vivo is limited by proteolysis or peptide transport into the ER, mice were immunized with recombinant vaccinia viruses containing mini-genes encoding antigenic peptides (bypassing the need for proteolysis), or these peptides with a NH2-terminal ER insertion sequence (bypassing the requirements for both proteolysis and transport). Additionally, mice were immunized with recombinant vaccinia viruses encoding rapidly degraded fragments of proteins. We report that limitations in induction of T(CD8+) responses vary among Ags: for some, full length proteins are as immunogenic as other forms tested; for others, maximal responses are induced by peptides or by peptides targeted to the ER. Most importantly, in every circumstance examined, targeting peptides to the ER never diminished, and in some cases greatly enhanced, the T(CD8+) immune response and provide an important alternative strategy in the design of live viral or naked DNA vaccines for the treatment of cancer and infectious diseases.
AB - CD8+ T lymphocytes (T(CD8+)) play an important role in cellular immune responses. T(CD8+) recognize MHC class I molecules complexed to peptides of 8 to 10 residues derived largely from cytosolic proteins. Proteins are generally thought to be fragmented in the cytoplasm and delivered to nascent class I molecules in the endoplasmic reticulum (ER) by a peptide transporter encoded by the MHC. To explore the extent to which T(CD8+) induction in vivo is limited by proteolysis or peptide transport into the ER, mice were immunized with recombinant vaccinia viruses containing mini-genes encoding antigenic peptides (bypassing the need for proteolysis), or these peptides with a NH2-terminal ER insertion sequence (bypassing the requirements for both proteolysis and transport). Additionally, mice were immunized with recombinant vaccinia viruses encoding rapidly degraded fragments of proteins. We report that limitations in induction of T(CD8+) responses vary among Ags: for some, full length proteins are as immunogenic as other forms tested; for others, maximal responses are induced by peptides or by peptides targeted to the ER. Most importantly, in every circumstance examined, targeting peptides to the ER never diminished, and in some cases greatly enhanced, the T(CD8+) immune response and provide an important alternative strategy in the design of live viral or naked DNA vaccines for the treatment of cancer and infectious diseases.
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M3 - Article
C2 - 7722298
AN - SCOPUS:0029057976
SN - 0022-1767
VL - 154
SP - 4414
EP - 4422
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -