Major Histocompatibility Complex Class II Expression Pathway (MHCII pathway)

The Major Histocompatibility Complex (MHC) Class II Expression Pathway is a fundamental biological process required for the presentation of exogenous antigens to CD4+ T lymphocytes (Roche & Furuta, 2015). This pathway is primarily regulated at the transcriptional level by the Class II Transactivator (CIITA), which coordinates the assembly of the RFX transcription factor complex on the highly conserved S-X-Y motifs of MHCII promoters (Reith et al., 2005). In the context of oncology, many cancers downregulate MHCII expression to achieve immune evasion, a process often mediated by epigenetic silencing or loss of CIITA (Axelrod et al., 2019). Conversely, the aberrant expression of MHCII on non-professional antigen-presenting cells is a hallmark of various autoimmune diseases, such as rheumatoid arthritis and type 1 diabetes (Handunnetthi et al., 2010). Therapeutic modulation of this pathway includes the use of Interferon-gamma to induce expression or Histone Deacetylase (HDAC) inhibitors to overcome epigenetic repression in tumor cells (Lee et al., 2017). Because this entry describes a complex biological pathway involving multiple discrete proteins rather than a single molecule or receptor, it is classified as an aggregate target.

Other names

HLA class II expression pathwayMHCII antigen presentation pathwayCIITA-mediated MHCII expressionMHC class II biosynthetic pathway

Transcriptional induction of the master regulator CIITA via IFN-gamma signaling or epigenetic modulation of MHCII promoters through HDAC inhibition to restore or suppress antigen presentation.