International Immunology, Vol 9, 81-89, Copyright © 1997 by Oxford University Press
WE Gillanders, HL Hanson, RJ Rubocki, TH Hansen and JM Connolly
We developed a novel approach to probe the molecular basis of TCR
recognition of the MHC class I-peptide complex and to determine how
constraints placed on peptide binding by the class I molecule influence T
cell recognition. We synthesized peptide pairs derived from the N- and
C-terminal regions of class I peptide ligands in which the TCR contacts and
dominant binding residues were placed together or were separated.
Complementary peptide pairs derived from two well- characterized Ld peptide
ligands, tum- (QNHRALDL) and p2Ca (LSPFPFDL), were tested for the ability
to sensitize targets for recognition by peptide-specific cytotoxic T
lymphocytes (CTL). The tum-derived tetramer QNHR, containing both primary
TCR contact residues (H17 and R18), is recognized only when used in
combination with ALDL which contains the primary binding residues (A19, D21
and L22). This suggests that both peptides of the pair contribute to
positioning of the TCR contacts. Remarkably, CTL clone P24 recognized
target cells sensitized with a trimer (QNH) combined with a pentamer
(RALDL), demonstrating that TCR recognition can occur when the TCR contacts
are separated (placed on separate peptide subunits). For the p2Ca peptide
LSPFPFDL, the C-terminal tetramer PFDL, which contains both the primary TCR
contact residue (P) and the dominant binding residue (L), is sufficient for
recognition. In addition, PFDL was able to bind effectively to Ld and to
activate naive antigen-specific T cells. These data suggest that peptide
subunits and complementary peptide pairs composed of trimeric, tetrameric
or pentameric peptides can bind independently to the Ld molecule in the
same register and orientation as they do when contained within the parent
peptide.
ARTICLES
Class I-restricted cytotoxic T cell recognition of split peptide ligands
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. A. Bowerman, L. A. Colf, K. C. Garcia, and D. M. Kranz Different Strategies Adopted by Kb and Ld to Generate T Cell Specificity Directed against Their Respective Bound Peptides J. Biol. Chem., November 20, 2009; 284(47): 32551 - 32561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Glithero, J. Tormo, K. Doering, M. Kojima, E. Y. Jones, and T. Elliott The Crystal Structure of H-2Db Complexed with a Partial Peptide Epitope Suggests a Major Histocompatibility Complex Class I Assembly Intermediate J. Biol. Chem., May 5, 2006; 281(18): 12699 - 12704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kageyama, T. J. Tsomides, N. Fukusen, I. A. Papayannopoulos, H. N. Eisen, and Y. Sykulev Potent Cytolytic Response by a CD8+ CTL Clone to Multiple Peptides from the Same Protein in Association with an Allogeneic Class I MHC Molecule J. Immunol., March 1, 2001; 166(5): 3028 - 3034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. C. Hornell, J. C. Solheim, N. B. Myers, W. E. Gillanders, G. K. Balendiran, T. H. Hansen, and J. M. Connolly Alloreactive and Syngeneic CTL Are Comparably Dependent on Interaction with MHC Class I {alpha}-Helical Residues J. Immunol., September 15, 1999; 163(6): 3217 - 3225. [Abstract] [Full Text] [PDF]
|
|