Tapasin is a facilitator, not an editor, of class I MHC peptide binding.
Tapasin has been proposed to function as a peptide editor to displace lower affinity peptides and/or to favor the binding of high affinity peptides. Consistent with this, cell surface HLA-B8 molecules in tapasin-deficient cells were less stable and the peptide repertoire was substantially altered. However, the binding affinities of peptides expressed in the absence of tapasin were unexpectedly higher, not lower. The peptide repertoire from cells expressing soluble tapasin was similar in both appearance and affinity to that presented in the presence of full-length tapasin, but the HLA-B8 molecules showed altered cell surface stability characteristics. Similarly, the binding affinities of HLA-A*0201-associated peptides from tapasin(+) and tapasin(-) cells were equivalent, although steady state HLA-A*0201 cell surface expression was decreased and the molecules demonstrated reduced cell surface stability on tapasin(-) cells. These data are inconsistent with a role for tapasin as a peptide editor. Instead, we propose that tapasin acts as a peptide facilitator. In this role, it stabilizes the peptide-free conformation of class I MHC molecules in the endoplasmic reticulum and thus increases the number and variety of peptides bound to class I MHC. Full-length tapasin then confers additional stability on class I MHC molecules that are already associated with peptides.
Zarling
Angela L
AL
Carter Immunology Center and Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
Luckey
Chance John
CJ
Marto
Jarrod A
JA
White
Forest M
FM
Brame
Cynthia J
CJ
Evans
Anne M
AM
Lehner
Paul J
PJ
Cresswell
Peter
P
Shabanowitz
Jeffrey
J
Hunt
Donald F
DF
Engelhard
Victor H
VH
D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D017920:Antiporters / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen; D015795:HLA-B8 Antigen / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017393:RNA Editing / Q000235:genetics / Q000276:immunology*; D020871:RNA Stability / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D017920:Antiporters; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015795:HLA-B8 Antigen; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D010446:Peptide Fragments; C107762:tapasin