Quantitative analysis of the immune response to mouse non-MHC transplantation antigens in vivo: The H60 histocompatibility antigen dominates over allothers

Minor histocompatibility Ags (minor H Ags) are substantial impediments to M HC-matched solid tissue and bone marrow transplantation. From an antigenic standpoint, transplantation between MHC-matched individuals has the potenti al to be remarkably complex. To determine the extent to which the immune re sponse is simplified by the phenomenon of immunodominance, we used peptide/ MHC tetramers based on recently discovered minor H Ags (H60, H13, and HY) a nd monitored in vivo CD8 T cell responses of female C57BL/6 mice primed wit h MHC-matched, but background-disparate, male BALB.B cells. CD8 T cells aga inst H60 overwhelmed responses to the H13 and HV throughout primary and sec ondary challenge. H60 inummodominance was an inherent quality, overcoming a lower memory precursor frequency compared with that of H13 and evoking a T cell response with diverse TCRV beta usage. IFN-gamma staining examining c ongenically defined minor H Ags extended H60 dominance over additional mino r H Ags, H28, H4, and H7. These four minor H Ags accounted for up to 85% of the CD8 T cell response, but H60 stood out as the major contributor. These findings show that immunodominance applies to antigenically complex transp lantation settings in vivo and that the responses to the H60 minor H Ag dom inates in this model. We suggest that immunodominant minor H Ags are those that result from the absence of a self analog.