Immunodominant CD4+ T cell receptor Vbeta repertoires involved in graft-versus-host disease responses to minor histocompatibility antigens.

Abstract

In vitro CTL responses to multiple minor histocompatibility Ags (miHA) are governed by immunodominance as demonstrated in the C57BL/6By (B6) anti-BALB.B strain combination. Immunodominance was also demonstrated to be operative in graft-vs-host disease (GVHD) responses against BALB.B-derived miHA following transplantation of B6 T cells into irradiated recipients of both the BALB.B and CXB recombinant inbred strains. The hierarchy of in vivo and in vitro T cell responses to miHA differed. GVHD did not develop in CXBG and CXBK mice, which express immunodominant miHA for CTL generation, whereas disease occurred in the BALB.B, CXBE, CXBI, and CXBJ mouse strains. Previous results demonstrated that B6 CD4+ T cells provide helper function for CD8+ T cells involved in GVHD responses in the BALB.B, CXBE, and CXBI strains. CD4+ T cells alone were mediators of GVHD in all strains except CXBE. This study analyzed the TCR Vbeta repertoires of CD4+ thoracic duct lymphocytes (TDL) collected during the initial stages of GVHD in the B6-->BALB.B and B6-->CXBE strain combinations. Positively selected CD4+ TDL from the B6-->BALB.B (B6(+BALB.B)) combination exhibited marked expansion in the TCR Vbeta6+ and Vbeta8.1/8.2+ families, as well as smaller increases in the Vbeta7 and Vbeta9 families. CD4+ TDL from the B6-->CXBE (B6(+CXBE)) combination displayed expansions in only the Vbeta7+ and Vbeta9+ families. These data suggest that B6 CD4+ T cells can recognize a limited number of immunodominant miHA during GVHD induction and that in both BALB.B and CXBE recipients, the TCR Vbeta repertoires partially overlap.