Expression of high levels of soluble allogeneic major histocompatability complex class i antigen by adenoviral gene transfer strongly inhibits allospecific cytotoxic t lymphocytes in vivo

2002 ◽  
Vol 34 (5) ◽  
pp. 1398-1399 ◽  
Author(s):  
C Graeb ◽  
M Justl ◽  
M.N Scherer ◽  
S Tange ◽  
E Frank ◽  
...  
Keyword(s):  
Gene Transfer ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatability Complex ◽  
Adenoviral Gene Transfer

scholarly journals Murine Cytotoxic T Lymphocytes Recognize an Epitope in an EBNA-1 Fragment, but Fail to Lyse EBNA-1–expressing Mouse Cells

1998 ◽  
Vol 187 (3) ◽  
pp. 445-450 ◽  
Author(s):  
Siddhartha Mukherjee ◽  
Pankaj Trivedi ◽  
David M. Dorfman ◽  
George Klein ◽  
Alain Townsend
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Deletion Mutant ◽  
Human Subjects ◽  
Full Length ◽  
Class I ◽  
Rich Region ◽  
Mouse Cells

Major histocompatibility complex class I–restricted cytotoxic T lymphocytes (CTLs) specific for epitopes within eight of the nine Epstein Barr Virus (EBV)-encoded latency-associated proteins have been recovered from EBV-infected human subjects by restimulation of lymphocytes in vitro. However, human class I–restricted CTL responses capable of recognizing EBNA-1 expressing cells were not detected in these studies. We have raised a murine CTL line that recognizes an epitope within EBNA-1 by immunizing mice with a vaccinia virus encoding a COOH-terminal EBNA-1 fragment. This novel CTL line was used to investigate whether the epitope (positions 509–517 in EBNA-1, presented through Kd) was presented to CTL by mouse cells expressing full-length EBNA-1 or a deletion mutant of EBNA-1, lacking the Glycine-Alanine (Gly-Ala)–rich region. Cells expressing full-length EBNA-1 are not lysed by the CTL line, whereas cells expressing the Gly-Ala deletion mutant are recognized. These results suggest that epitopes from full-length EBNA-1 are poorly presented, and that the Gly-Ala–rich region is responsible for this phenomenon. The inefficient presentation of EBNA-1–derived epitopes may explain the absence or rarity of EBNA-1–specific CTLs in vivo, a strategy that may allow EBV to maintain persistence within the immunocompetent host without being eliminated by CTLs.

scholarly journals Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes.

1992 ◽  
Vol 175 (2) ◽  
pp. 481-487 ◽  
Author(s):  
L C Eisenlohr ◽  
J W Yewdell ◽  
J R Bennink
Keyword(s):  
Influenza Virus ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Class I ◽  
Sufficient Information ◽  
Complex Molecules ◽  
Histocompatibility Complex ◽  
Flanking Sequences

Cytotoxic T lymphocytes (CTL) recognize class I major histocompatibility complex molecules complexed to peptides of eight to nine residues generated from cytosolic proteins. We find that CTL recognize, in vitro and in vivo, cells synthesizing a 10-residue peptide consisting of an initiating methionine followed by nine residues corresponding to a naturally processed determinant from influenza virus nucleoprotein (NP) (residues 147-155). Addition of two COOH-terminal residues corresponding to NP residues 157 and 158 severely reduced presentation of the endogenously produced peptide to CTL in vitro and in vivo. Extension of NH2 and COOH terminal flanking residues to include residues corresponding to NP residues 137-146 and 159-168 failed to increase the antigenicity of this peptide. Its presentation was greatly enhanced, however, by further extending the NH2 and COOH termini to include all of the additional residues of NP. These findings indicate first, that a naturally processed viral ligand (with an NH2-terminal Met) of a class I molecule contains sufficient information to access intracellular class I molecules, and second, that flanking residues can influence the processing and presentation of antigens to CTL.

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