Unique Biochemical Properties of Human Leukocyte Antigen-E Allow for a Highly Specific Function in Immune Recognition

PROBLEM: Does a correlation exist between the expression of human leukocyte antigen (HLA) class Ia and HLA-E and what is its biological significance? METHOD OF STUDY: 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 β2-microglobulin to investigate TAP dependence of the cell-surface expression of HLA-E. RESULTS: 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. CONCLUSIONS: 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.