Cross-reactivity of cytomegalovirus-specific CD8+ T cells to allo-major histocompatibility complex class I molecules.
BACKGROUND
In transplantation settings, cytomegalovirus (CMV) infection is a common complication. CMV infection is associated with a higher incidence of graft rejection in solid organ transplantation and graft-versus-host disease in bone marrow transplantation. The underlying mechanism of this association could be the generation of CMV-specific CD8 T cells capable of cross-reacting with alloantigens present on graft and host, respectively.


METHODS
Whereas as to date, no direct ex vivo analysis can be performed of the CD8 T-cell repertoire directed at allo-major histocompatibility complex (MHC) class I molecules, virus-specific cells can be readily enumerated by use of MHC-peptide tetrameric complexes. In this study, the authors used this technique to analyze potential overlapping CD8 T-cell repertoires between self-MHC-viral peptide and allo-MHC complexes by stimulating CMV-specific CD8 T cells with alloantigens. RESULTS.: The authors found that CMV-specific CD8 T cells are activated and proliferate on stimulation with alloantigens.


CONCLUSIONS
Although these cells are cytotoxic against CMV-peptide pulsed target cells, no cytotoxicity of CMV-specific cells to alloantigens could be detected, inferring that there are other mechanisms of graft damage by alloantigen-stimulated virus-specific CTL.
Gamadia
Laila E
LE
Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center G1-106, University of Amsterdam, PO Box 1100 DD Amsterdam, The Netherlands. l.e.gamadia@amc.uva.nl
Remmerswaal
Ester B
EB
Surachno
Sugianto
S
Lardy
Neubury M
NM
Wertheim-van Dillen
Pauline M
PM
van Lier
René A W
RA
ten Berge
Ineke J M
IJ
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D003587:Cytomegalovirus / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex
D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens