Table II.

Mechanisms of Impaired MHC Class I Expression

A Irreversible or “hard” genetic lesions: Not recovered by IFN treatment structural alterations • Total, locus‐ or allele‐specific loss of the MHC class I HC • LOH of the MHC class I HC • Mutations, deletions, recombinations of β2‐m • Structural alterations in LMP2, TAP1, TAP2, and tpn Other molecular defects • Methylation of MHC class I HC, β2‐m, tpn, CIITA genes • Posttranscriptional downregulation of MHC class I antigens and APM components • Posttranslational effects of TAP (phosphorylation) • Defects in the MHC class I export • Impaired IFN signaling B Reversible or “soft” lesions: Recoverable after IFNs treatment • Transcriptional downregulation of MHC class I HC gene expression • Selective MHC locus downregulation • Transcriptional downregulation of APM components