HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ib protein with a restricted expression pattern.
HLA-F is currently the most enigmatic of the human MHC-encoded class Ib genes. We have investigated the expression of HLA-F using a specific Ab raised against a synthetic peptide corresponding to amino acids 61-84 in the alpha1 domain of the predicted HLA-F protein. HLA-F is expressed as a beta2-microglobulin-associated, 42-kDa protein that shows a restricted tissue distribution. To date, we have detected this product only in peripheral blood B cells, B cell lines, and tissues containing B cells, in particular adult tonsil and fetal liver, a major site of B cell development. Thermostability assays suggest that HLA-F is expressed as an empty heterodimer devoid of peptide. Consistent with this, studies using endoglycosidase-H and cell surface immunoprecipitations also indicate that the overwhelming majority of HLA-F contains an immature oligosaccharide component and is expressed inside the cell. We have found that IFN-gamma treatment induces expression of HLA-F mRNA and HLA-F protein, but that this does not result in concomitant cell surface expression. HLA-F associates with at least two components of the conventional class I assembly pathway, calreticulin and TAP. The unusual characteristics of the predicted peptide-binding groove together with the predominantly intracellular localization raise the possibility that HLA-F may be capable of binding only a restricted set of peptides.
Wainwright
S D
SD
Department of Clinical Medicine, Division of Obstetrics and Gynaecology, University of Bristol, St. Michael's Hospital, United Kingdom.
Biro
P A
PA
Holmes
C H
CH
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000328:Adult; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism*; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D014407:Tumor Cells, Cultured
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D006680:HLA Antigens; C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C073119:TAP1 protein, human; D007371:Interferon-gamma