일시: 2009-05-18 11:00 ~ 12:00
발표자: 서울대학교 의과대학 의과학과 최은영 교수
담당교수: 이현숙
장소: 500동 다목적회의실 (목암홀)
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. 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. H60-specific memory CD8 T cells generated during a helped primary response vigorously expanded only when re-challenged under helped conditions. The help-requirement for an optimal secondary response was confirmed by a reduction in peak size by CD4-depletion, and was reproduced after skin-transplantation. Helpless conditions or non-cognate separate-help during the secondary response resulted in a significant reduction in the peak size and different response kinetics. Re-providing CD4 help during a tertiary challenge restored robust memory expansion; however, the repeated deprivation of help further reduced clonal expansion. Adoptively transferred memory CD8 T cells did not proliferate in CD40L-/- hosts. In the CD40-/- hosts, marginal memory expansion was detected after priming with male H60-cells but was completely abolished by priming with peptide-loaded CD40-/- cells, suggesting the essential role of CD40 and CD40L in memory responses. These results provide insight into the control of minor H antigen-specific CD8 T cell responses, to maximize the graft-versus-leukemia response. 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. And the CD4 help is related to the diversity of TCRs involved in H60-specific CD8 T cell responses. These results provide insight into the control of minor H antigen-specific CD8 T cell responses, to maximize the graft-versus-leukemia response.