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HLA-target antigens and T-cell receptor diversity of activated T cells
invading the skin during acute graft-versus-host disease
J Gaschet, MA Trevino, M Cherel, R Vivien, A Garcia-Sahuquillo, MM Hallet, M Bonneville, JL Harrousseau, R Bragado, N Milpied and H Vie
Institut National de la Sante et de la Recherche Medicale (Unite 211),
Nantes, France.
To study the repertoire and specificity of T lymphocytes infiltrating skin
lesions during graft-versus-host disease (GVHD), we performed an exhaustive
molecular and functional analysis of 146 T-cell clones derived from the
skin of three patients undergoing an acute GVHD after allogeneic bone
marrow transplantation (BMT) from HLA-mismatched related donors. Analysis
of T-cell receptor (TCR) rearrangement and TCR chain junctional sequences
demonstrated the presence of 11 distinct clones among the 64 derived from
patient UPN1, six among the 58 derived from patient UPN2, and seven among
the 24 derived from patient UPN3. Three of the 11 T-cell clones from
patient UPN1, and all clones from patients UPN2 and UPN3 reacted with
mismatched HLA alleles between the bone-marrow donor and recipient.
Moreover, both HLA class I (HLA-A2 and -B27) and class II (HLA DP101,
DP401, DP1301, DQ8, and DR402) molecules were recognized during this early
antihost response. Finally, both TCR alpha and beta chains turned out to be
extremely diverse, even within populations of clones derived from the same
patient and directed against the same HLA allele. Taken together, these
results indicate that any HLA mismatch is potentially targeted during early
GVHD, and that the T-cell response at the onset of GVHD is both oligoclonal
and highly diversified.
Volume 87,
Issue 6,
pp. 2345-2353,
03/15/1996
Copyright © 1996 by The American Society of Hematology
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