Real-time T-cell profiling identifies H60 as a major minor histocompatibility antigen in murine graft-versus-host disease.
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.
Choi
Eun Young
EY
Jackson Laboratory, Bar Harbor, ME 04609, USA.
Christianson
Gregory J
GJ
Yoshimura
Yoshitaka
Y
Jung
Nadja
N
Sproule
Thomas J
TJ
Malarkannan
Subramaniam
S
Joyce
Sebastian
S
Roopenian
Derry C
DC
D000818:Animals; D020296:Animals, Congenic; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006648:Histocompatibility; D016056:Immunodominant Epitopes / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009928:Organ Specificity; D011828:Radiation Chimera; D012307:Risk Factors; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016056:Immunodominant Epitopes; D015778:Minor Histocompatibility Antigens; C114735:minor H antigen H60