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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-05-1299.

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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4259-4264

PLENARY PAPER

Real-time T-cell profiling identifies H60 as a major minor histocompatibility antigen in murine graft-versus-host disease

Eun Young Choi, Gregory J. Christianson, Yoshitaka Yoshimura, Nadja Jung, Thomas J. Sproule, Subramaniam Malarkannan, Sebastian Joyce, and Derry C. Roopenian

From the Jackson Laboratory, Bar Harbor, ME; Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN; and Department of Medicine, Blood Research Institute, Milwaukee, WI.

Although CD8 T cells are thought to be a principal effector population of graft-versus-host disease (GVHD), their dynamics and specificity remain a mystery. Using a mouse model in which donor and recipient were incompatible at many minor histocompatibility antigens (minor H Ags), the CD8 T-cell response was tracked temporally and spatially through the course of GVHD. Donor CD8 T cells in the circulation, spleen, lung, and liver demonstrated virtually identical kinetics: rapid expansion and then decline prior to morbidity. Remarkably, up to one fourth of the CD8 T cells were directed against a single minor antigen, H60. Extreme H60 immunodominance occurred regardless of sampling time, site, and genetic background. This study is the first to analyze the T cells participating in GVHD in "real-time," demonstrates the exceptional degree to which immunodominance of H60 can occur, and suggests that such superdominant minor H Ags could be risk factors for GVHD.

© 2002 by The American Society of Hematology.
 

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