A single residue exchange within a viral CTL epitope alters proteasome-mediated degradation resulting in lack of antigen presentation

F. Ossendorp; M Eggers; A Neisig; Thomas Ruppert; M Groettrup; A Sijts; E Mengedë; Peter M Kloetzel; J. Neefjes; U Koszinowski; C.J. Melief

A single residue exchange within a viral CTL epitope alters proteasome-mediated degradation resulting in lack of antigen presentation

F. Ossendorp, M Eggers, A Neisig, Thomas Ruppert, M Groettrup, A Sijts, E Mengedë, Peter M Kloetzel, J. Neefjes, U Koszinowski, C.J. Melief

Department of Immunohematology, Academic Hospital Leiden, The Netherlands.

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

CTL epitope (KSPWFTTL) encoded by AKV/MCF type of murine leukemia virus (MuLV) differs from the sequence in Friend/Moloney/Rauscher (FMR) type in one residue (RSPWFTTL). CTL experiments indicated defective processing of the FMR peptide in tumor cells. Proteasome-mediated digestion of AKV/MCF-type 26-mer peptides resulted in the early generation and higher levels of epitope-containing fragments than digestion of FMR-type peptides, explained by prominent cleavage next to R in the FMR sequence. The fragments were identified as 10- and 11-mer peptides and were efficiently translocated by TAP. The naturally presented AKV/MCF peptide is the 8-mer, indicating ER peptide trimming. In conclusion, a single residue exchange can cause CTL epitope destruction by specific proteasomal cleavage.

Original language	English
Pages (from-to)	115-24
Number of pages	10
Journal	Immunity
Volume	5
Issue number	2
Publication status	Published - Aug 1996

Keywords

ATP-Binding Cassette Transporters
Amino Acid Sequence
Animals
Antigen Presentation
Antigens, Viral, Tumor
Cysteine Endopeptidases
Epitopes
Glycoproteins
Kinetics
Leukemia Virus, Murine
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Multienzyme Complexes
Peptide Fragments
Proteasome Endopeptidase Complex
T-Lymphocytes, Cytotoxic
Tumor Cells, Cultured
Journal Article
Research Support, Non-U.S. Gov't

Cite this

@article{37451e086bd344df912dcf2f94c0aff6,

title = "A single residue exchange within a viral CTL epitope alters proteasome-mediated degradation resulting in lack of antigen presentation",

abstract = "CTL epitope (KSPWFTTL) encoded by AKV/MCF type of murine leukemia virus (MuLV) differs from the sequence in Friend/Moloney/Rauscher (FMR) type in one residue (RSPWFTTL). CTL experiments indicated defective processing of the FMR peptide in tumor cells. Proteasome-mediated digestion of AKV/MCF-type 26-mer peptides resulted in the early generation and higher levels of epitope-containing fragments than digestion of FMR-type peptides, explained by prominent cleavage next to R in the FMR sequence. The fragments were identified as 10- and 11-mer peptides and were efficiently translocated by TAP. The naturally presented AKV/MCF peptide is the 8-mer, indicating ER peptide trimming. In conclusion, a single residue exchange can cause CTL epitope destruction by specific proteasomal cleavage.",

keywords = "ATP-Binding Cassette Transporters, Amino Acid Sequence, Animals, Antigen Presentation, Antigens, Viral, Tumor, Cysteine Endopeptidases, Epitopes, Glycoproteins, Kinetics, Leukemia Virus, Murine, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Multienzyme Complexes, Peptide Fragments, Proteasome Endopeptidase Complex, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured, Journal Article, Research Support, Non-U.S. Gov't",

author = "F. Ossendorp and M Eggers and A Neisig and Thomas Ruppert and M Groettrup and A Sijts and E Menged{\"e} and Kloetzel, {Peter M} and J. Neefjes and U Koszinowski and C.J. Melief",

year = "1996",

month = aug,

language = "English",

volume = "5",

pages = "115--24",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - A single residue exchange within a viral CTL epitope alters proteasome-mediated degradation resulting in lack of antigen presentation

AU - Ossendorp, F.

AU - Eggers, M

AU - Neisig, A

AU - Ruppert, Thomas

AU - Groettrup, M

AU - Sijts, A

AU - Mengedë, E

AU - Kloetzel, Peter M

AU - Neefjes, J.

AU - Koszinowski, U

AU - Melief, C.J.

PY - 1996/8

Y1 - 1996/8

N2 - CTL epitope (KSPWFTTL) encoded by AKV/MCF type of murine leukemia virus (MuLV) differs from the sequence in Friend/Moloney/Rauscher (FMR) type in one residue (RSPWFTTL). CTL experiments indicated defective processing of the FMR peptide in tumor cells. Proteasome-mediated digestion of AKV/MCF-type 26-mer peptides resulted in the early generation and higher levels of epitope-containing fragments than digestion of FMR-type peptides, explained by prominent cleavage next to R in the FMR sequence. The fragments were identified as 10- and 11-mer peptides and were efficiently translocated by TAP. The naturally presented AKV/MCF peptide is the 8-mer, indicating ER peptide trimming. In conclusion, a single residue exchange can cause CTL epitope destruction by specific proteasomal cleavage.

AB - CTL epitope (KSPWFTTL) encoded by AKV/MCF type of murine leukemia virus (MuLV) differs from the sequence in Friend/Moloney/Rauscher (FMR) type in one residue (RSPWFTTL). CTL experiments indicated defective processing of the FMR peptide in tumor cells. Proteasome-mediated digestion of AKV/MCF-type 26-mer peptides resulted in the early generation and higher levels of epitope-containing fragments than digestion of FMR-type peptides, explained by prominent cleavage next to R in the FMR sequence. The fragments were identified as 10- and 11-mer peptides and were efficiently translocated by TAP. The naturally presented AKV/MCF peptide is the 8-mer, indicating ER peptide trimming. In conclusion, a single residue exchange can cause CTL epitope destruction by specific proteasomal cleavage.

KW - ATP-Binding Cassette Transporters

KW - Amino Acid Sequence

KW - Animals

KW - Antigen Presentation

KW - Antigens, Viral, Tumor

KW - Cysteine Endopeptidases

KW - Epitopes

KW - Glycoproteins

KW - Kinetics

KW - Leukemia Virus, Murine

KW - Mice

KW - Mice, Inbred C57BL

KW - Molecular Sequence Data

KW - Multienzyme Complexes

KW - Peptide Fragments

KW - Proteasome Endopeptidase Complex

KW - T-Lymphocytes, Cytotoxic

KW - Tumor Cells, Cultured

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Article

C2 - 8769475

SN - 1074-7613

VL - 5

SP - 115

EP - 124

JO - Immunity

JF - Immunity

IS - 2

ER -

A single residue exchange within a viral CTL epitope alters proteasome-mediated degradation resulting in lack of antigen presentation

Abstract

Keywords

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