Characterization and functional aspects of HLA class Ib molecules in skin cancer

Anna Maria Bordoy & Meghan Sand Bengtsson

Studenteropgave: Speciale

Abstrakt

The Human Leukocyte Antigen (HLA) class Ib molecules consist of three molecules – HLA-E, HLA-F and HLA-G [reviewed in Kochan et al., 2013]. HLA-G and HLA-F were first reported to be expressed by trophoblast cells in combination with HLA-E at the feto-maternal interface, where they protect the fetus against maternal immune attacks [reviewed in Hviid, 2006]. Later, it was observed that tumor cells also express HLA-G and this lead to the hypothesis that expression of HLA-G was a mechanism by which tumors could escape the immune system and immunosurveillance [Paul et al., 1998]. HLA-E and HLA-F are also often found over-expressed in a variety of malignancies [reviewed in Kochan et al., 2013]. In this thesis, we characterized the HLA class Ib mRNA and protein expression of seven malignant melanoma cell lines by Droplet Digital PCR and flow cytometry, respectively. The mRNA expression of different isoforms of HLA-G was further characterized by RT-PCR fragment length analysis. Messenger RNA expression of HLA class Ib was observed in all cell lines while protein expression was observed in some of these. The levels of mRNA and protein expression differed between the cell lines. HLA-G is the most extensively studied HLA class Ib molecule. Less is known about the function of HLA-E, while the function of HLA-F remains largely unknown. The function of HLA-E seems to be mainly through inhibition of NK and CD8+ T cells, while the function of HLA-G seems to be diverse [reviewed in Kochan et al., 2013]. One mechanism whereby HLA-G is thought to induce immune tolerance is through induction of regulatory T cells (Tregs). In this thesis, we performed functional pilot studies in which we co-cultured peripheral blood mononuclear cells (PBMCs) with malignant melanoma cell lines. In some cases, it seemed that the percentages of Tregs and of HLA-G-positive T cells were affected by the co-culture. In addition, we performed a pilot study investigating if the peripheral blood levels of Tregs and HLA-G-positive T cells were different between skin cancer patients and healthy individuals. The levels of Tregs did not differ between the two groups but the level of HLA-G-positive CD4+ T cells seemed to be increased while the level of HLA-G-positive CD8+ T cells seemed to be decreased in the peripheral blood of skin cancer patients compared to healthy individuals. However, additional studies have to be performed to confirm or disconfirm the findings of these pilot studies.

UddannelserMolekylærbiologi, (Bachelor/kandidatuddannelse) KandidatMedicinalbiologi, (Bachelor/kandidatuddannelse) Kandidat
SprogEngelsk
Udgivelsesdato1 aug. 2014

Emneord

  • Tregs
  • HLA class Ib
  • Immunosurveillance
  • Cancer