title: Magnitude of alloresponses to MHC class I/II expressing human cardiac myocytes is limited by their intrinsic ability to process and present antigenic peptides.
abstract: In this investigation we have explored the relationship between the weak allogenicity of cardiac myocytes and their capacity to present allo-antigens by examining the ability of a human cardiac myocyte cell line (W-1) to process and present nominal antigens. W-1 cells (HLA-A*0201 and HLA-DR beta1*0301) pulsed with the influenza A matrix 1 (58-66) peptide (M1) were able to serve as targets for the HLA-A*0201 restricted CTL line PG, specific for M1-peptide. However, PG-CTLs were unable to lyse W-1 target cells infected with a recombinant vaccinia virus expressing the M1 protein (M1-VAC). Pretreatment of these M1-VAC targets with IFN-gamma partially restored their ability to process and present the M1 peptide. However, parallel studies demonstrated that IFN-gamma pretreated W-1's could not process tetanus toxin (TT) or present the TT(830-843) peptide to HLA-DR3 restricted TT-primed T cells. Semi-quantitative RT-PCR measurements revealed significantly lower constitutive levels of expression for MHC class I, TAP-1/2, and LMP-2/7 genes in W-1s that could be elevated by pretreatment with IFN-gamma to values equal to or greater than those expressed in EBV-PBLs. However, mRNA levels for the genes encoding MHC class II, Ii, CIITA, and DMA/B were markedly lower in both untreated and IFN-gamma pretreated W-1s relative to EBV-PBLs. Furthermore, pulse-chase analysis of the corresponding genes revealed significantly lower protein levels and longer half-life expression in W-1s relative to EBV-PBLs. These results suggest that weak allogenicity of cardiac myocytes may be governed by their limited expression of MHC genes and gene products critical for antigen processing and presentation.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: J Bruce
authors.initials: JB
authors.lastname: Sundstrom
authors.forename: Kimberley C
authors.initials: KC
authors.lastname: Jollow
authors.forename: Veronique
authors.initials: V
authors.lastname: Braud
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: E Clinton
authors.initials: EC
authors.lastname: Lawrencec
authors.forename: Edwin W
authors.initials: EW
authors.lastname: Ades
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D012333:RNA, Messenger