Nonclassical behavior of the thymus leukemia antigen: peptide transporter-independent expression of a nonclassical class I molecule.
The thymus leukemia (TL) antigen is a major histocompatibility complex-encoded nonclassical class I molecule. Here we present data demonstrating that expression of the TL antigen, unlike other class I molecules, is completely independent of the function of the transporter associated with antigen processing (TAP). The TL antigen is expressed by transfected TAP-2-deficient RMA-S cells when these cells are grown at 37 degrees C. In transfected RMA cells, the kinetics of arrival of TL antigen on the cell surface are similar to those of a classical class I molecule. The kinetics are not altered in TAP-deficient RMA-S cells, demonstrating that surface TL expression in TAP-deficient cells is not due to the stable expression of a few molecules that leak out by a TAP-independent pathway. Soluble TL molecules produced by Drosophila melanogaster cells are highly resistant to thermal denaturation, unlike peptide-free classical class I molecules synthesized by these insect cells. In addition, these soluble TL molecules are devoid of detectable bound peptides. The results demonstrate that the TL antigen is capable of reaching the surface without bound peptide, although acquisition of peptide or some other ligand through a TAP-independent pathway cannot be formally excluded. We speculate that the ability of the TL antigen to reach the cell surface, under conditions in which other class I molecules do not, may be related to a specialized function of the TL molecule in the mucosal immune system, and possibly in the stimulation of intestinal gamma delta T cells.
Holcombe
H R
HR
Department of Microbiology & Immunology, University of California, Los Angeles School of Medicine 90024, USA.
Castaño
A R
AR
Cheroutre
H
H
Teitell
M
M
Maher
J K
JK
Peterson
P A
PA
Kronenberg
M
M
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000199:Actins / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D001692:Biological Transport; D018076:DNA, Complementary / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D005813:Genes, Synthetic; D005822:Genetic Vectors; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000502:physiology; D010455:Peptides / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D011489:Protein Denaturation; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000235:genetics
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000199:Actins; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C489516:Tap2 protein, mouse; D001613:beta 2-Microglobulin; C028388:thymus-leukemia antigens; C071692:TAP2 protein, human; D008668:Metallothionein