Studies on the antigenicity of the NKG2D ligand H60a in tumour cells

Abstract

Summary H60a is a minor histocompatibility antigen expressed in BALB and 129/Sv but not C57BL/6 mouse strains. The majority of CD8+ T cells in C57BL/6 mice responding to BALB.B splenocytes are specific for H60a. Interestingly, H60a is expressed constitutively on tumour cells, but its nature as a tumour rejection antigen, as a parallel to its function as a transplant rejection antigen, has not been studied. In this report, we show that tumour cells that constitutively express H60a at the cell surface can be recognized by H60a‐specific T cells. Furthermore, when H60a‐expressing sarcoma cell lines are transplanted into C57BL/6 mice, H60a‐specific T cells can be found at high percentages among the tumour‐infiltrating CD8+ T cells. These findings were seen in C57BL/6 but not F1 (C57BL/6 × 129) mice (which express H60a), suggesting that endogenous tolerance mechanisms suppress the antigenic properties of H60a. Our findings have implications for the generation of tumour vaccines against human natural killer group 2D ligands, such as MHC class I chain‐like gene A, that are also transplantation antigens.

The nuclear factor‐κB pathway down‐regulates expression of the NKG2D ligand H60a in vitro: implications for use of nuclear factor‐κB inhibitors in cancer therapy

“…H60a (minor histocompatibility antigen 60a) is an NKG2D ligand that binds to NKG2D with high affinity and activates NK cell lysis . We recently found that H60a can act as a tumour antigen in allogeneic but not syngeneic systems, hence activating H60a‐specific CD8 + T cells . As a target of both T and NK cells, H60a undergoes cancer immuno‐editing such that tumours that arise in immune‐deficient mice generally have higher levels of H60a than tumours that arise in wild‐type mice .…”

“…17 We recently found that H60a can act as a tumour antigen in allogeneic but not syngeneic systems, hence activating H60a-specific CD8 + T cells. 18 As a target of both T and NK cells, H60a undergoes cancer immuno-editing such that tumours that arise in immune-deficient mice generally have higher levels of H60a than tumours that arise in wild-type mice. 6 It is not known how tumour cells decrease their level of H60a to evade immune recognition.…”