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

• Published in: American journal of reproductive immunology (1989) 1998-09, Vol.40 (3), p.177-182
• Main Authors: WEISS, ELISABETH H., CANNICH, ASTRID, SPRINKS, MATTHEW, FERNANDEZ, NELSON, ULBRECHT, MATTHIAS
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal; Antigen presentation; Antigens; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histocompatibility antigens (hla, h-2 and other systems); Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; HLA Antigens - biosynthesis; HLA Antigens - genetics; HLA Antigens - immunology; HLA-E; HLA-E Antigens; Humans; Isoelectric Focusing; Mice; Molecular immunology; peptides; Precipitin Tests; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sensitivity and Specificity; Transfection; β2-microglobulin
• ISSN: 1046-7408; 8755-8920; 1600-0897
• DOI: 10.1111/j.1600-0897.1998.tb00410.x

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‐con‐trolled 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.