Distinct functions of tapasin revealed by polymorphism in MHC class I peptide loading.
Peptide assembly with class I molecules is orchestrated by multiple chaperones including tapasin, which bridges class I molecules with the TAP and is critical for efficient Ag presentation. In this paper, we show that, although constitutive levels of endogenous murine tapasin apparently are sufficient to form stable and long-lived complexes between the human HLA-B*4402 (B*4402) and mouse TAP proteins, this does not result in normal peptide loading and surface expression of B*4402 molecules on mouse APC. However, increased expression of murine tapasin, but not of the human TAP proteins, does restore normal cell surface expression of B*4402 and efficient presentation of viral Ags to CTL. High levels of soluble murine tapasin, which do not bridge TAP and class I molecules, still restore normal surface expression of B*4402 in the tapasin-deficient human cell line 721.220. These findings indicate distinct roles for tapasin in class I peptide loading. First, tapasin-mediated bridging of TAP-class I complexes, which despite being conserved across the human-mouse species barrier, is not necessarily sufficient for peptide loading. Second, tapasin mediates a function which probably involves stabilization of empty class I molecules and which is sensitive to structural compatibility of components within the loading complex. These discrete functions of tapasin predict limitations to the study of HLA molecules across some polymorphic and species barriers.
Peh
C A
CA
Department of Immunology, Allergy and Arthritis, Flinders University of South Australia, Bedford Park.
Laham
N
N
Burrows
S R
SR
Zhu
Y
Y
McCluskey
J
J
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000502:physiology; D000483:Alleles; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D017920:Antiporters / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059948:HLA-B44 Antigen; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D026901:Membrane Transport Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000276:immunology*; D012995:Solubility; D014162:Transfection; D014407:Tumor Cells, Cultured
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000276:Adjuvants, Immunologic; D017920:Antiporters; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D010455:Peptides; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C107762:tapasin