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Magnitude of Alloresponses to MHC Class I/II Expressing Human Cardiac Myocytes is Limited by their Intrinsic Ability to Process and Present Antigenic Peptides

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Author(s): J. Bruce Sundstrom | Kimberley C. Jollow | Veronique Braud | Francois Villinger | Andrew J. McMichael | E. Clinton Lawrence | Edwin W. Ades | Aftab A. Ansari

Journal: Clinical and Developmental Immunology
ISSN 1740-2522

Volume: 10;
Issue: 2-4;
Start page: 213;
Date: 2003;
Original page

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 β1*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-γ partially restored their ability to process and present the M1 peptide. However, parallel studies demonstrated that IFN-γ 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-γ 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-γ 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.

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