HLA-TARGET ANTIGENS AND T-CELL RECEPTOR DIVERSITY OF ACTIVATED T-CELLS INVADING THE SKIN DURING ACUTE GRAFT-VERSUS-HOST DISEASE

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 deri ved from the skin of three patients undergoing an acute GVHD after all ogeneic 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 a mong the 64 derived from patient UPN1, six among the 58 derived from p atient UPN2, and seven among the 24 derived from patient UPN3. Three o f the 11 T-cell clones from patient UPN1. and all clones from patients UPN2 and UPN3 reacted with mismatched HLA alleles between the bone-ma rrow donor and recipient. Moreover, both HLA class I (HLA-A2 and -B27) and class II (HLA DP101. DP401. DP1301, DO8, and DR402) molecules wer e recognized during this early antihost response. Finally, both TCR al pha and beta chains turned out to be extremely diverse, even within po pulations 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 div ersified. (C) 1996 by The American Society of Hematology.