S. Malarkannan et al., ALLOREACTIVE CD8(-CELLS CAN RECOGNIZE UNUSUAL, RARE, AND UNIQUE PROCESSED PEPTIDE() T)MHC COMPLEXES/, The Journal of immunology, 157(10), 1996, pp. 4464-4473
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.