Rapid turnover of HLA proteins in quiescent lymphocytes: proposed connection with immunologic surveillance

Current immunologic theory defines a role for HLA-A, -B, -C proteins in cells presenting foreign antigens to cytotoxic T lymphocytes. No clear function, however, is assigned to the prominently represented HLA molecules on the T cells themselves. To investigate this question, the synthesis and turnover of HLA-A, -B, -C molecules in human peripheral lymphocytes was studied. Newly synthesized HLA-A, -B, -C and beta 2-microglobulin molecules were identified among total lymphocyte proteins by two-dimensional gel electrophoresis and specific immunoselection. In resting T lymphocytes, the polymorphic set of HLA-A, -B, -C proteins was among the most prominently synthesized and rapidly turned over of total cell proteins. Its half-life was 6 to 7 hr, which is considerably shorter than that of total cell protein. HLA and beta 2M were the major proteins of the plasma membrane undergoing active synthesis and turnover in resting T lymphocytes. After growth stimulation, the rate of HLA synthesis increased to a lesser degree than total protein synthesis. Survival of newly synthesized HLA was increased, however, indicating reduction in HLA turnover. The result was the accumulation of HLA in the plasma membrane. It is suggested that continuous degradation and replacement reflects the biochemical nature of the participation of HLA molecules in immunologic surveillance by quiescent lymphocytes. Cessation of HLA turnover, with accumulation of surface HLA molecules, is a biochemical adjustment related to T cell activation.