| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Microbiology and Immunology and
Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461
Vesicular stomatitis virus (VSV) elicits
H-2Kb-restricted CTLs specific for the immunodominant VSV
octapeptide RGYVYQGL. To study the structural features important for
interaction between the TCR ß-chain and the peptide/MHC complex, we
immunized TCR 
-chain transgenic mice with the VSV peptide and raised
a panel of anti-VSV CTL clones with identical TCR -chains.
Consistent with our previous analysis of uncloned populations of
primary CTLs, the anti-VSV CTL clones were all Vß13+
and expressed TCR ß-chains with highly homologous
complementarity-determining region 3 (CDR3) loops. Although the clones
expressed similar TCRs, they differed in their ability to cross-react
with VSV peptide variants singly substituted at TCR contact positions 4
and 6. These findings allowed us to identify short stretches of amino
acids in the C-terminal region of the CDR3ß loop that, when altered,
modify the cross-reaction capability of the TCR to position 4 and
position 6 variant peptides. To further probe the structural correlates
of biologic cross-reactivity, we used cross-reactive CTL clones and
cell lines expressing point mutations in H-2Kb to
investigate the effect of single amino acid changes in the peptide on
the pattern of recognition of the TCR for the peptide/MHC complex.
Single conservative substitutions in the peptide were sufficient to
alter the recognition contacts between a cross-reactive TCR and the MHC
molecule, supporting the idea that the TCR can make overall structural
adjustments in MHC contacts to accommodate single amino acid changes in
the peptide.
This article has been cited by other articles:
|
|
 |
|
  J. Lustgarten, A. L. Dominguez, and C. Pinilla Identification of Cross-Reactive Peptides Using Combinatorial Libraries Circumvents Tolerance against Her-2/neu-Immunodominant Epitope J. Immunol., February 1, 2006; 176(3): 1796 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Mullins, T. N. J. Bullock, T. A. Colella, V. V. Robila, and V. H. Engelhard Immune Responses to the HLA-A*0201-Restricted Epitopes of Tyrosinase and Glycoprotein 100 Enable Control of Melanoma Outgrowth in HLA-A*0201-Transgenic Mice J. Immunol., November 1, 2001; 167(9): 4853 - 4860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Honda, W. Zhang, A. M. Kalergis, T. P. DiLorenzo, F. Wang, and S. G. Nathenson Hapten Addition to an MHC Class I-Binding Peptide Causes Substantial Adjustments of the TCR Structure of the Responding CD8+ T Cells J. Immunol., October 15, 2001; 167(8): 4276 - 4285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhang, S. Honda, F. Wang, T. P. DiLorenzo, A. M. Kalergis, D. A. Ostrov, and S. G. Nathenson Immunobiological Analysis of TCR Single-Chain Transgenic Mice Reveals New Possibilities for Interaction between CDR3{alpha} and an Antigenic Peptide Bound to MHC Class I J. Immunol., October 15, 2001; 167(8): 4396 - 4404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. Thomson, A. M. Kalergis, J. C. Sacchettini, and S. G. Nathenson A Structural Difference Limited to One Residue of the Antigenic Peptide Can Profoundly Alter the Biological Outcome of the TCR-Peptide/MHC Class I Interaction J. Immunol., March 15, 2001; 166(6): 3994 - 3997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Rosa, R. Krishnan, S. Markel, J. P. Schneck, R. Houghten, C. Pinilla, and D. J. Diamond Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from positional scanning synthetic combinatorial libraries Blood, March 15, 2001; 97(6): 1776 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Baker, R. V. Turner, S. J. Gagnon, D. C. Wiley, and W. E. Biddison Identification of a Crucial Energetic Footprint on the {alpha}1 Helix of Human Histocompatibility Leukocyte Antigen (Hla)-A2 That Provides Functional Interactions for Recognition by Tax Peptide/Hla-A2-Specific T Cell Receptors J. Exp. Med., March 5, 2001; 193(5): 551 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Garcia-Peydro, A. Paradela, J. P. Albar, and J. A. L. d. Castro Antagonism of Direct Alloreactivity of an HLA-B27-Specific CTL Clone by Altered Peptide Ligands of Its Natural Epitope J. Immunol., November 15, 2000; 165(10): 5680 - 5685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Kalergis and S. G. Nathenson Altered Peptide Ligand-Mediated TCR Antagonism Can Be Modulated by a Change in a Single Amino Acid Residue Within the CDR3{beta} of an MHC Class I-Restricted TCR J. Immunol., July 1, 2000; 165(1): 280 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Gagne, S. Brouard, M. Giral, F. Sebille, A. Moreau, M. Guillet, J.-D. Bignon, B.-M. Imbert, M.-C. Cuturi, and J.-P. Soulillou Highly Altered V{beta} Repertoire of T Cells Infiltrating Long-Term Rejected Kidney Allografts J. Immunol., February 1, 2000; 164(3): 1553 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Kalergis, T. Ono, F. Wang, T. P. DiLorenzo, S. Honda, and S. G. Nathenson Single Amino Acid Replacements in an Antigenic Peptide Are Sufficient to Alter the TCR V{beta} Repertoire of the Responding CD8+ Cytotoxic Lymphocyte Population J. Immunol., June 15, 1999; 162(12): 7263 - 7270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Loftus, E. Huseby, P. Gopaul, C. Beeson, and J. Goverman Highly Cross-Reactive T Cell Responses to Myelin Basic Protein Epitopes Reveal a Nonpredictable Form of TCR Degeneracy J. Immunol., June 1, 1999; 162(11): 6451 - 6457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hudrisier, J. Riond, O. Burlet-Schiltz, M. G. von Herrath, H. Lewicki, B. Monsarrat, M. B. A. Oldstone, and J. E. Gairin Structural and Functional Identification of Major Histocompatibility Complex Class I-restricted Self-peptides as Naturally Occurring Molecular Mimics of Viral Antigens. POSSIBLE ROLE IN CD8+ T CELL-MEDIATED, VIRUS-INDUCED AUTOIMMUNE DISEASE J. Biol. Chem., May 25, 2001; 276(22): 19396 - 19403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Sharma, J. J. Kuhns, S. Yan, R. H. Friedline, B. Long, R. Tisch, and E. J. Collins Class I Major Histocompatibility Complex Anchor Substitutions Alter the Conformation of T Cell Receptor Contacts J. Biol. Chem., June 8, 2001; 276(24): 21443 - 21449. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
