The peptide-specific alloreactive human T cell repertoire varies largely between individuals and is not extended in HLA-A*0205-anti-HLA-A*0201 pairings

Alloreactive T cells recognize framework or peptide-dependent determinants on foreign MHC molecules. Among the peptide-dependent alloreactive T cells a significant proportion is specific for one particular peptide presented b y the allo-MHC molecule as antigen-specific T cells would do. Such alloreac tive, peptide-specific T cells are referred to as 'allorestricted'. High-av idity HLA-A*02 allorestricted cytotoxic T lymphocyte (CTL) clones specific for peptide libraries can be generated from HLA-A*02- donors. We made use o f this technique to study the role of closely related self-HLA molecules on shaping of the alloreactive T cell repertoire. Peripheral blood lymphocyte s from HLA-A*0205 individuals were stimulated by HLA-A*0201 targets pulsed with an HLA-A*0201 peptide library. We did not observe a bias towards pepti de-specific CTL in the HLA-A*0201-directed alloreactive repertoire of HLA-A *0205 donors as compared to HLA-A*02- donors. Comparison of the alloreactiv e T cell response between two donors having similar HLA haplotypes demonstr ated that the allorestricted T cell repertoire is largely different between individuals.