Factors influencing the patterns of T lymphocyte allorecognition.

Background: Strong alloreactive T cell responses are a menace in transplantation surgery and their menagement requires understanding the basis of alloreactivity. Alloantigen recognition can be peptide independent, peptide specific, or peptide dependent. The mechanisms influencing each recognition pattern are largely unknown.

Methods: Peptide dependence was examined in vitro by adding peptides to antigen processing-deficient cell line used as target in cytotoxic T cell assays. Responses to major histocompatibility complex (MHC) alleles most homologous to self were recently shown to be more peptide dependent than to those with lesser homology to self. Hence, peptide reactivity in vivo was estimated based on relative strengths of alloreactive responses to more homologous and less homologous MHC alleles.

Results: Alloreactive CD8+ TCR repertoire in beta2-microglobulin-deficient mice is preferentially peptide independent. The peptide-specific component is acquired as a function of wild-type thymic epithelium grafting. Irrespective of the presence of the peptide-specific component, in vivo alloantigenic priming was associated with a greater sensitivity to the MHC structure than was in vitro priming.

Conclusions: Thymic positive selection and the mode of alloreactivity induction are the major independent factors determining the patterns of alloantigen recognition.