ALLOREACTIVE CD8(-CELLS CAN RECOGNIZE UNUSUAL, RARE, AND UNIQUE PROCESSED PEPTIDE() T)MHC COMPLEXES/

The identity and abundance of self-peptide/MHC class I complexes that serve as ligands for alloreactive T cells remain largely unknown. Usin g the K-b-restricted, alloreactive T cells as a probe, the Ag precurso r gene, adenosine phosphoribosyl transferase (APRT), was isolated by e xpression cloning, its naturally processed product was identified as t he SLVELTSL (SEL8) octapeptide, The SEL8 peptide shared five residues with the previously identified SVVEFSSL (JAL8) peptide that stimulated the same T cell, but lacked the critical phenylalanine/tyrosine resid ue at the primary p5 anchor position, Despite the absence of this key conserved anchor residue, SEL8 was bound tightly by K-b MHC and yet wa s expressed at less than 10 copies/cell, Mutations in the donor APRT g ene in the APC caused a concomitant loss in the ability of APCs to sti mulate T cells, The results confirm that the display of peptide/MHC co mplexes in cells exceeds the predictions based upon consensus motifs, and that CD8(+) alloreactive and conventional Ag-specific T cells are indistinguishable in their ability to recognize unique and rare peptid e/MHC class I complexes.