Interindividual conservation of T-cell receptor beta chain variable regions by minor histocompatibility antigen-specific HLA-A*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 (TCR) 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.
Goulmy
E
E
Department of Immunohaematology and Blood Bank, University Hospital Leiden, The Netherlands.
Pool
J
J
van den Elsen
P J
PJ
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006086:Graft vs Host Disease / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D018076:DNA, Complementary; D015234:HLA-A Antigens; D015778:Minor Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta