Title

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

Document Type

Article

Publication Date

2002

Keywords

Animals-Congenic, Bone-Marrow-Transplantation, CD8-Positive-T-Lymphocytes, Female, Flow-Cytometry, Graft-vs-Host-Disease, Histocompatibility, Immunodominant-Epitopes, Liver, Lung, Mice, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Minor-Histocompatibility-Antigens, Organ-Specificity, Radiation-Chimera, Risk-Factors, Specific-Pathogen-Free-Organisms, Spleen, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocyte-Subsets

JAX Source

Blood 2002 Dec; 100(13):4259-65.

Grant

AI28802/AI/NIAID, HL54977/HL/NHLBI, R01HL56579/HL/NHLBI

Abstract

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.