Different regulation of MHC class I antigen processing components in human tumors.

Abstract

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.

• Authors: Barbara Seliger
• Journal: Journal of immunotoxicology (J Immunotoxicol) Vol. 5 Issue 4 Pg. 361-7 (Oct 2008) ISSN: 1547-6901 [Electronic] England
• PMID: 19404870 (Publication Type: Journal Article, Review)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 2
• ATP-Binding Cassette Transporters
• Histocompatibility Antigens Class I
• TAP1 protein, human
• beta 2-Microglobulin
• Peptide Hydrolases
• Proteasome Endopeptidase Complex

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 2
• ATP-Binding Cassette Transporters (physiology)
• Antigen Presentation (immunology)
• Down-Regulation (immunology)
• Histocompatibility Antigens Class I (immunology)
• Humans
• Neoplasms (immunology, physiopathology)
• Peptide Hydrolases (physiology)
• Proteasome Endopeptidase Complex (physiology)
• beta 2-Microglobulin (physiology)