A transcription factor interacting with the class I gene enhancer is inactive in tumorigenic cell lines which suppress major histocompatibility complex class I genes.

Abstract

AKR leukemias display different amounts of major histocompatibility complex class I antigens on the cell surface. The absence of H-2Kk molecules correlates with the ability of these cell lines to form tumors in vivo as well as to escape lysis by cytotoxic T lymphocytes in vitro. In this report it is shown that the 5' regulatory area of the H-2Kk gene failed to activate transcription in H-2Kk-negative cells. Examination of the proteins interacting with the H-2Kk enhancer in expressing and nonexpressing cells revealed clear differences. In particular, the level of a nuclear protein interacting at position -166 was greatly reduced in the negative cell lines. A transcription factor, known as H2TF1 or KBF1, has been shown previously to interact with this binding site and to be essential for the expression of certain class I genes as well as the expression of beta 2-microglobulin. These results demonstrate that the molecular mechanism of class I gene suppression in malignant tumor cells is at the level of transcription and is most probably modulated by H2TF1/KBFI. In addition, it is shown that the same transcription factor is only present in mouse tissues expressing class I antigens.

Altered binding of regulatory factors to HLA class I enhancer sequence in human tumor cell lines lacking class I antigen expression.

“…P2m expression, (ii) defects in assembly or peptide loading (24), and (iii) regulatory defects as described by Henseling et al (25), Lenardo et al (26), and this paper.…”

Developmental and tissue-specific expression of the Q5 k gene

“…Therefore, while classical class I antigen expression is often reduced or even absent (K k-and D k-expression in some AKR leukemias ( Fig. 3; Henseling et al 1990), and in primary AKR thymomas (data not shown) Q5 k expression seems to be augmented in the transformed tissue respectively cell lines. Thus, the Q5 k gene product might represent the novel H-2 class I "allo" specificity, characterized by Labeta and co-workers (1989) on Q5 ~ expressing tumor cell lines.…”

Major Histocompatibility Complex Modulation and Loss

“…Altered binding of regulatory factors to the MHC class I HC gene enhancer element by methylation or changes in the chromatin structure results in MHC class I HC mRNA down-regulation and consequently in a reduced expression of these molecules on the cell surface ( Fig. 5.9) [52,53].…”