title: Alloreactive cytotoxic T lymphocytes focus on specific major histocompatibility complex-bound peptides.
abstract: Alloreactive T cells are often specific for individual peptides that are bound to allogeneic major histocompatibility complex (MHC) molecules. Other alloreactive T cells are reported to be peptide-independent or to recognize MHC conformational changes that are induced by multiple peptides. We tested 12 anti-HLA-B7 alloreactive cytotoxic T lymphocyte (CTL) clones that bind a restricted region of HLA-B7, including three CTL clones that were generated in a protocol designed to stimulate peptide-independent T cells. All 12 CTLs recognized multiple point mutations in the HLA-B7 peptide-binding groove. Eleven of the 12 CTLs recognized specific peptides that eluted in one or two fractions on high-performance liquid chromatography (HPLC). None of the CTLs promiscuously recognized 16 HLA-B7-binding synthetic peptides, although one CTL recognized minor by-products in one synthetic peptide preparation. CTL clone KID-9 cross-reacted with allogeneic HLA-B7 and HLA-B27 molecules and recognized a distinct peptide bound to each MHC molecule. CTL clone KD-11 recognized peptides that eluted in two HPLC fractions and recognized HLA-B7-transfected peptide antigen processing defective T2 cells. These results indicate that CTL allorecognition is peptide-specific whether the allogeneic MHC molecules are expressed on normal cells or antigen processing-deficient cells.
authors.affiliation: Department of Pathology, the university of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Smith
authors.forename: E
authors.initials: E
authors.lastname: Huczko
authors.forename: V H
authors.initials: VH
authors.lastname: Engelhard
authors.forename: Y Y
authors.initials: YY
authors.lastname: Li
authors.forename: C T
authors.initials: CT
authors.lastname: Lutz
mesh_terms: D017951:Antigen Presentation; D002999:Clone Cells / Q000276:immunology; D015793:HLA-B7 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008285:Major Histocompatibility Complex / Q000502:physiology*; D009154:Mutation; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015793:HLA-B7 Antigen; D010455:Peptides