Characterization of CD8 T response to dominant mouse minor histocompatibility antigen, H60

다국어 초록 (Multilingual Abstract)

Minor histocompatibility antigens(minor H Ags) are substantial impediments to MHC-matched solid tissue and bone marrow transplantation. From an antigenic standpoint, transplantation between MHC-matched individuals has the potential to be remarkably complex. However, the extent of the immune response is simplified by the phenomenon of immunodominance. Among the dominant minor H Ags identified, H60 stood out as the major contributor, accounting for majority up to 85% of the CD8 T cell response with over additional minor H Ags, H28, H4, and H7. In the H60-specific response, T cells with various TCR usages were involved, as confirmed by the spectratying of T cells isolated using H60 peptide/ MHC I tetramer. As a response to cellular antigen, CD8 T cell response specific for H60 is CD4-derived help dependent, requiring CD4 T cell activation not only for induction of the CD8 response, but also for secondary response to occur. Moreover, the absence of CD4 help at the induction stage of the primary response derived the CD8 specific for H60 to be tolerized, which could not be reverted by providing CD4 help during the secondary response. The tolerance induction of CD8 T cells specific for H60 did not render the CD8 T cells reactive to subdominant minor H Ags to take over the place, super-dominancy, played by H60 originally. Understanding the characteristics of T cells involved in dominant antigen, H60, specific response has important implications in tissue transplantation and vaccine design.