Overlap of direct and indirect alloreactive T-cell repertoires when MHC polymorphism is limited to the peptide binding groove

The immune response to allogeneic-MHC molecules can be divided into two pathways based on the nature of the antigen. In the direct pathway, T cells respond to intact allogeneic MHC molecules, while in the indirect pathway T cells respond to alto MHC-derived peptides presented by self-MHC. The T-cell repertoire used in the direct and indirect alloresponse have not been compared in the same alloantigen. system. Here, HLA-DR transgenic mice are used to compare. the repertoires of T cells that respond to the same alloantigen through either the direct or the indirect pathway. Separate direct and indirect DR1 anti-DR4 T-cell lines were generated and the T cell repertoire was analyzed by molecular methods. The same six Vbeta families were involved in both direct and indirect cultures indicating a complete overlap in the Vbeta gene usage. A partial overlap at the clonotype level was observed as two identical clonotypic TCRs were observed in both direct and indirect cultures. Interestingly, the T cells observed in both cultures were public as the same TCRs were identified in cultures developed from independent mice. These results raise the prospect that immune suppression of selected T cells during allo-transplantation can simultaneously modulate direct and indirect alloreactivities. Human Immunology 63, 91-100 (2002). (C) American Society for Histocompatibility and Immunogenetics, 2002. Published by Elsevier Science Inc.