Effects of thymic selection on T cell recognition of foreign and tumor antigenic peptides.
The graft-versus-leukemia (GVL) effect associated with allogeneic blood and marrow transplantation has largely been a clinically described phenomenon until recently. We are beginning to understand the cellular and molecular nature of GVL, and in this review the authors highlight the potential for self-antigen-specific T lymphocytes to contribute to GVL. The authors focus on myeloid tissue-restricted proteins as GVL target antigens in CML and AML, and in particular on proteinase 3 and other azurophil granule proteins as targets for both autologous and allogeneic T-cell responses. Finally, the authors discuss myeloid self-antigen-directed alloreactivity in the context of our evolving understanding of the critical molecular determinants of allogeneic T-cell recognition. By altering T-cell receptor affinity, peptide specificity can be maintained and the potency of immunity can be enhanced in the MHC-mismatched setting.