T-cell receptor Vα usage by effector CD4+Vβ11+ T cells mediating graft-versus-host disease directed to minor histocompatibility antigens

T-cell receptor (TCR) V alpha (TRAV) and V beta (TRBV) chains provide the T-cell specificity for recognition of major histocompatibility complex (MHC)-bound antigens. However, there is limited information on the diversity of TRAV use within an antigen response. Previous investigation of CD4(+) T-cell-mediated graft-versus-host disease (GVHD) in the minor histocompatibility antigen-mismatched C57BL/6 (136)-->BALB.B irradiated murine model determined that V beta 11(+) T cells were associated with disease severity. Polymerase chain reaction (PCR)-based complementarity-determining region 3 (CDR3)-sized spectratype analysis of B6 V beta 11(+) T cells from the spleens of recipient BALB.B mice undergoing GVHD indicated biased use within the V alpha 6, 9, 13, 14, 18, and 22 families. To probe deeper into this limited V alpha response, the current study was undertaken to further define TRAV-J alpha (TRAJ) nucleotide sequences found in host-presensitized B6 V beta 11(+) T cells proliferating in response to in vitro stimulation with BALB.B splenocytes. Using the nonpalindromic adaptor PCR method, we found dominant use of the TRAV13-TRAJ16 transcript combination. Then, using laser capture microdissection, we found use of the identical TRAV-TRAJ nucleotide sequence in areas dominated by infiltrating V beta 11(+) CD4(+) T cells during the development of GVHD in both the rete-like prominences of the dorsal lingual epithelium and the ileal crypts of the small intestine. (C) 2007 American, Society for Blood and Marrow Transplantation.