REPERTOIRE ANALYSIS OF CD8(-CELL RESPONSES TO MINOR HISTOCOMPATIBILITY ANTIGENS INVOLVED IN GRAFT-VERSUS-HOST DISEASE() T)

Graft-vs-host disease (GVHD) is a major complication of allogeneic bon e marrow transplantation. Experimentally, lethal GVHD can be induced i n MHC-matched strain combinations differing in expression of multiple minor histocompatibility Ags (miHA), Recently, the GVHD potential of C 57BL/6By (B6) T cells in irradiated BALB.B (both H2(b)) and related CX B recombinant inbred strains of mice has been studied to determine the scope of the response to miHA in vivo and how it compared with CTL re sponses to immunodominant miHA in vitro, The GVHD response in these st rain combinations appeared to be limited to a few Ags, yet there was n o correlation of these miHA with that of in vitro CTL responses. To fu rther investigate the role of CD8(+) T cells in GVHD, we analyzed posi tively selected miHA-specific donor CD8(+) thoracic duct lymphocytes ( TDL) collected from irradiated BALB.B and CXBE mice, 5 to 6 days after transplantation of B6 T cells. Flow cytometric analysis of B6--> BALB .B TDL did not indicate expansion of any particular TCR V beta family, whereas V beta 10 and V beta 14 families were significantly expanded in the B6--> CXBE TDL. However, PCR-based complementarity-determining region 3 size spectratyping revealed overlapping involvement of donor V beta 1, 6, 8, 9, 10, and 14 families in both BALB,B and CXBE recipie nts and unique utilization of the V beta 4 family in BALB.B mice, sugg esting oligoclonal T cell responses to a limited number of miHA, In ad dition, the injection of CD8(+)V beta 14(+) B6 T cells into irradiated BALB,B and CXBE mice induced lethal GVHD, confirming the involvement of miHA-specific T cells within an individual V beta family.