INTERINDIVIDUAL CONSERVATION OF T-CELL RECEPTOR-BETA CHAIN VARIABLE REGIONS BY MINOR HISTOCOMPATIBILITY ANTIGEN-SPECIFIC HLA-A-ASTERISK-0201-RESTRICTED CYTOTOXIC T-CELL CLONES

Minor histocompatibility antigens (mHags) are involved in the induction of graft-versus-host disease (GVHD) after HLA-identical bone marrow transplantation. Previously, we isolated a series of HLA-A*0201-restricted cytotoxic T-cell (CTL) clones specific for the same mHag HA-1 from peripheral blood of three unrelated patients who were suffering from GVHD, We have now analyzed the composition of the T-cell receptor (ICR) V regions of 12 of these mHag HA-1-specific HLA-A*0201-restricted CTL clones by DNA sequencing of the alpha and beta chains, Of these 12 clones, derived from three unrelated individuals, five independent TCR alpha V- and beta V-region sequences were established, The TCR alpha chains were composed of varying TCR alpha V and TCR alpha J genes with no obvious similarities in structure in the N regions. However, the TCR beta chains all used the TCR beta V6S9 gene segment, and showed remarkable similarities within the N-D-N regions; ie, three independent beta-chain sequences (originating from donors Ha and Gy) shared a leucine/valine amino acid pair, whereas the other two (originating from donors Ha and Wi) shared a serine/threonine pair, all at positions 99 and 100 of the TCR beta V region, In conclusion, the TCR analysis of HA-1 mHag-specific CTL clones has shown that the HA-1 mHag/ HLA-A*0201 complex selects for highly similar TCR beta V regions, (C) 1995 by The American Society of Hematology.