Alloreactive T cell recognition of the HLA-DR beta N-terminal polymorphic region

T cell alloreactivity, originally discovered as a tissue transplantation effect, is believed to be a manifestation of the normal major histocompatibility complex (MHC) restriction of antigen presentation by accessory cells to T cells. The molecular features of the human class II-MHC proteins (HLA) which are recognized by alloreactive T cells are not at present understood, although they are clearly related to the polymorphic nature of the MHC proteins. Human CD4+ T cell clones were selected by response to the HLA-DR2 peptides beta 1-15 or beta 51-65, in an MHC-restricted manner. In addition, these clones respond to cell lines expressing the DR2 haplotype, without the requirement for accessory antigen presenting cells. DR2 beta peptide 1-15 blocks the T cell alloresponse and polymorphic residues are shown to stimulate the peptide-specific response of these clones. Thus, the polymorphic residues contained within the DR beta sequence 1-15 are demonstrated to be directly recognized by alloreactive T cells.