MHC class I-related chain A and B ligands are differentially expressed in human cervical cancer cell lines

Here we show that MICA and MICB exhibit differential expression patterns among HPV-infected (SiHa and HeLa) and non-infected cell lines (C33-A, a tumor cell line, and HaCaT, an immortalized keratinocyte cell line). Cell surface expression of MICA was higher than cell surface expression of MICB in the HPV-positive cell lines; in contrast, HPV-negative cells expressed lower levels of MICA. Interestingly, the MICA levels observed in C33-A cells were overcome by significantly higher MICB expression. Also, all cell lines released higher amounts of soluble MICB than of soluble MICA into the cell culture supernatant, although this was most pronounced in C33-A cells. Additionally, Real-Time PCR analysis demonstrated that MICA was strongly upregulated after genotoxic stress.This study provides evidence that even when MICA and MICB share a high degree of homology at both genomic and protein levels, differential regulation of their expression and cell surface appearance might be occurring in cervical cancer-derived cells.The immune system endows vertebrates with the ability to detect and respond to various challenges to the homeostasis of the organism; among these, is the emergence of nascent tumors. NK cells are major innate effectors for the early recognition of transformed cells because they can spontaneously detect their targets without prior sensitization [1]. The killing activity is mainly controlled by an exquisite balance of competing inhibitory and activating receptors [2,3]. One of the best characterized activating receptors is NKG2D, a C-type lectin-like activating immunoreceptor whose expression is confined to NK cells, CD8+ T cells and γδ T cells [4,5]. More recently, the expression of NKG2D has been described also in a small population of CD4+CD28- T cells in patients with autoimmune conditions [6]. In humans, NKG2D recognizes two structurally distinct families of ligands named MHC class I chain-related (MIC) molecules, and the UL16-binding proteins (ULBPs) 1 to