ABSTRACT

Chronic graft-versus-host disease (GVHD) is a complex disease, probably most similar in biology to the autoimmune disease Systemic Lupus Erythematosus with the major exception that alloreactive donor-derived T cells induce the disease. GVHD results from alloreactivity of donor T lymphocytes against recipient cells. T lymphocytes recognize peptide antigens in the context of human leukocyte antigen (HLA) molecules. Exogenous proteins are endocytosed by antigen-presenting cells (APC) and transported to lysosomes where acid hydrolases cleave the protein into peptides. These peptides are then loaded into HLA class II molecules and transported to the cell surface for presentation to CD4CT lymphocytes. Endogenous antigens are processed and presented using similar end major histocompatibility complex (MHC) class II pathways (1). Endogenous peptides associate with class I HLA molecules in the Golgi apparatus of APC and are presented to CD8CT lymphocytes (2-6). Alloreactivity also requires costimulatory signals from APC, including the secretion of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a) (7).