Duration of alloantigen presentation and avidity of T cell antigen recognition correlate with immunodominance of CTL response to minor histocompatibility antigens.
CD8 T lymphocytes (CTL) responsive to immunodominant minor histocompatibility (minor H) Ags are thought to play a disproportionate role in allograft rejection in MHC-identical solid and bone marrow transplant settings. Although many studies have addressed the mechanisms underlying immunodominance in models of infectious diseases, cancer immunotherapy, and allograft immunity, key issues regarding the molecular basis of immunodominance remain poorly understood. In this study, we exploit the minor H Ag system to understand the relationship of the various biochemical parameters of Ag presentation and recognition to immunodominance. We show that the duration of individual minor H Ag presentation and the avidity of T cell Ag recognition influence the magnitude and, hence, the immunodominance of the CTL response to minor H Ags. These properties of CTL Ag presentation and recognition that contribute to immunodominance have implications not only for tissue transplantation, but also for autoimmunity and tumor vaccine design.
Yoshimura
Yoshitaka
Y
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. sebastian.joyce@vanderbuilt.edu
Yadav
Rajwardhan
R
Christianson
Gregory J
GJ
Ajayi
Wilfred U
WU
Roopenian
Derry C
DC
Joyce
Sebastian
S
D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
D007519:Isoantigens; D015778:Minor Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell