Unique biochemical properties of human leukocyte antigen-E allow for a highly specific function in immune recognition.

Abstract

Does a correlation exist between the expression of human leukocyte antigen (HLA) class Ia and HLA-E and what is its biological significance? HLA-E transcripts were detected by reverse transcriptase-polymerase chain reaction. Metabolically labeled HLA-E heavy chains were immunoprecipited and analyzed by one-dimensional isoelectric focusing. Mouse RMA-S cells defective with regard to transporter associated with antigen processing (TAP) function were transfected with HLA-E and human beta 2-microglobulin to investigate TAP dependence of the cell-surface expression of HLA-E. HLA-E is transcribed regardless of the down-regulation of polymorphic HLA class Ia expression. HLA-E is transported to the cell surface in the absence of TAP-controlled peptide loading. In human cells, the amount of HLA-E protein is very low regardless of the presence of correct peptide ligands. HLA-E regulates immune functions in cells that have down-regulated the expression of polymorphic HLA-class Ia molecules, either by preventing harmful natural killer cells from attacking targets that have physiologically decreased HLA-class Ia expression or by activating effector cells against virus-infected and tumor cells with impaired HLA-class Ia expression.