| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Surgery, University of Glasgow, Scotland, United Kingdom
Recent studies in the rat have identified a role for T
cell-dependent alloantibody in rejection of MHC class I-disparate
allografts. RT1Aa-disparate PVG.R8 heart grafts are
rejected acutely in naive, and hyperacutely in sensitized,
PVG.RT1u recipients by CD4 T cell-dependent alloantibody.
Here, we examined the T cell Ag recognition pathways responsible and
show that direct injection into skeletal muscle of plasmid DNA,
encoding a water-soluble form of the RT1Aa MHC class I
heavy chain (pcmu-tAa), stimulates IgG2b cytotoxic
alloantibody and markedly accelerates rejection of PVG.R8 heart grafts
(median survival time 2 days). pcmu-tAa injection did not
induce CTL to Aa, arguing against direct allorecognition of
soluble Aa. Treatment with mAbs confirmed that the
alloimmune response to pcmu-tAa injection depended on CD4,
not CD8, T cells. Priming T cells for indirect allorecognition by
injection of 15-mer peptides spanning the 
1 and 2 domains of
Aa failed to stimulate anti-Aa Ab but
caused an accelerated Ab response to a PVG.R8 heart and a modest
acceleration in graft rejection (median survival time 4 days). These
results suggest that both soluble MHC class I and allopeptides prime
CD4 T cells by the indirect pathway, but that soluble class I is a more
effective immunogen for humoral alloimmunity because its tertiary
protein structure provides B cell epitopes. We propose that priming
humoral alloimmunity, like CTL priming, requires recognition of intact
MHC on donor cells, but essential T cell help can be provided by CD4 T
cells recognizing allogeneic class I exclusively by the indirect
pathway.
This article has been cited by other articles:
|
|
 |
|
  C. J. Callaghan, F. J. Rouhani, M. C. Negus, A. J. Curry, E. M. Bolton, J. A. Bradley, and G. J. Pettigrew Abrogation of Antibody-Mediated Allograft Rejection by Regulatory CD4 T Cells with Indirect Allospecificity J. Immunol., February 15, 2007; 178(4): 2221 - 2228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Higuchi, T. Maruyama, A. Jaramillo, and T. Mohanakumar Induction of Obliterative Airway Disease in Murine Tracheal Allografts by CD8+ CTLs Recognizing a Single Minor Histocompatibility Antigen J. Immunol., February 15, 2005; 174(4): 1871 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lovegrove, G. J. Pettigrew, E. M. Bolton, and J. A. Bradley Epitope Mapping of the Indirect T Cell Response to Allogeneic Class I MHC: Sequences Shared by Donor and Recipient MHC May Prime T Cells That Provide Help for Alloantibody Production J. Immunol., October 15, 2001; 167(8): 4338 - 4344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Heidler, K. Baker, K. Woods, C. Schnizlein-Bick, O. W. Cummings, R. Sidner, B. Foresman, and D. S. Wilkes Instillation of Allogeneic Lung Antigen-Presenting Cells Deficient in Expression of Major Histocompatibility Complex Class I or II Antigens Have Differential Effects on Local Cellular and Humoral Immunity and on Pathology in Recipient Murine Lungs Am. J. Respir. Cell Mol. Biol., October 1, 2000; 23(4): 499 - 505. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. I. Reznik, A. Jaramillo, L. Zhang, G. A. Patterson, J. D. Cooper, and T. Mohanakumar ANTI-HLA ANTIBODY BINDING TO HLA CLASS I MOLECULES INDUCES PROLIFERATION OF AIRWAY EPITHELIAL CELLS: A POTENTIAL MECHANISM FOR BRONCHIOLITIS OBLITERANS SYNDROME J. Thorac. Cardiovasc. Surg., January 1, 2000; 119(1): 39 - 45. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
