Different regulation of MHC class I antigen processing components in human tumors.
In recent years, progress has been made in understanding how peptides presented by MHC Class I molecules were generated, in particular which proteases are involved in this process and how intracellular pathways influence antigen presentation in professional antigen-presenting cells and various types of tumor cells. This review will give an overview of MHC Class I abnormalities in malignancies and their underlying molecular mechanisms. Dependent on the tumor types structural alterations in particular of the MHC Class I heavy chain, beta(2)-m and the TAP1 subunit have been found at a low frequency, whereas dysregulation of MHC Class I antigen processing components appears to be the major mechanism of MHC Class I down-regulation in tumors of distinct origin. This could occur at the epigenetic, transcriptional and/or post-transcriptional level. The lack or suppression of MHC Class I surface expression due to antigen-processing deficiencies are accompanied by reduced recognition and lysis by antigen-specific cytotoxic T-lymphocytes, which is further often associated with disease progression.
Seliger
Barbara
B
Martin-Luther-Universitat Halle-Wittenberg, Institute of Medical Immunology, Halle (Saale), Germany. barbara.seliger@medizin.uni-halle.de
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D017951:Antigen Presentation / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000276:immunology* / Q000503:physiopathology*; D010447:Peptide Hydrolases / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D001613:beta 2-Microglobulin / Q000502:physiology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex