Binding of human β2-microglobulin to murine EL4 thymoma cells upregulates MHC class I heavy-chain epitopes, inhibits IL-2 secretion and induces resistance to killing by natural killer cells

Abstract

A variety of murine tumor cell lines was studied for its binding of exogeneously added human β 2-microglobulin (h β 2m). Three T lymphomas and one IL-2-dependent T-cell line (HT-1) bound substantial amounts of h β 2m, whereas P815 mastocytoma cells, an Abelson virus-infected pre-B cell line (ABLS-8), X63 B-lymphoma cells and YAC cells did not bind h β 2m. In two of the T lymphomas, EL4 and BW5147, binding of h β 2m led to an increase in major histocompatibility complex class I (MHC-I) heavy-chain epitope expression as measured by anti-H-2K/D antibody binding and FACS analysis. EL4 cells which had bound h β 2m decreased their rate of constitutive IL-2 secretion and became resistant to activated natural killer (NK) cell killing. The present data suggest that binding of h β 2m to mouse T cells leads to conformational changes of MHC-I heavy chains which influence both effector and target functions of the cell.