title: Allogeneic MHC class I molecules with numerous sequence differences do not elicit a CTL response.
abstract: CD8+ T cell-mediated alloreactivity is generally believed to involve recognition of the alpha1/alpha2 domains of donor-type class I MHC molecules as well as the peptides they bind. Using the CTLp assay outcome as a parameter for the induction of alloreactivity, we have retrospectively surveyed 80 haematopoietic stem cell donor/patient pairs that feature a range of allelic differences at single HLA-A, -B, and -C loci in an attempt to probe the predictive value of such mismatches. In contrast to the expectation that greater degree of allelic disparity would lead to more alloreactivity, we found that in a substantial number of cases, class I MHC molecules with numerous sequence differences did not elicit an allogeneic CTL response. We propose that in generating a T cell repertoire with a sufficiently narrow responsive for self-MHC, positive thymic selection limits the capacity to recognize allogeneic MHC molecules whose structure and sequence have diverged extensively. These findings are important for donor and patient MHC matching strategies and our understanding of T cell-MHC interaction after haematopoietic stem cell transplantation.
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martin B A
authors.initials: MB
authors.lastname: Heemskerk
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Marlies K A
authors.initials: MK
authors.lastname: Dankers
authors.forename: Jon J
authors.initials: JJ
authors.lastname: van Rood
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
mesh_terms: D019943:Amino Acid Substitution; D020137:Base Pair Mismatch; D003601:Cytotoxicity Tests, Immunologic; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I