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* Department of Microbiology and Immunology and
Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620
A single residue polymorphism distinguishes HLA-B*4402(D116) from HLA-B*4405(Y116), which was suggested to allow HLA-B*4405 to acquire peptides without binding to tapasin-TAP complexes. We show that HLA-B*4405 is not inherently unable to associate with tapasin-TAP complexes. Under conditions of peptide deficiency, both allotypes bound efficiently to TAP and tapasin, and furthermore, random nonamer peptides conferred higher thermostability to HLA-B*4405 than to HLA-B*4402. Correspondingly, under conditions of peptide sufficiency, more rapid peptide-loading, dissociation from TAP complexes, and endoplasmic reticulum exit were observed for HLA-B*4405, whereas HLA-B*4402 showed greater endoplasmic reticulum retention and enhanced tapasin-TAP binding. Together, these studies suggest that position 116 HLA polymorphisms influence peptide occupancy, which in turn determines binding to tapasin and TAP. Relative to HLA-B*4405, inefficient peptide loading of HLA-B*4402 is likely to underlie its stronger tapasin dependence for cell surface expression and thermostability, and its enhanced susceptibility to pathogen interference strategies.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant AI44115 (to M.R.) from the National Institutes of Health, fellowships from the American Heart Association (to V.T. and G.R.), and financial support from the Michigan Diabetes Research and Training Center and the University of Michigan Rheumatic Diseases Core Center.
2 Address correspondence and reprint requests to Dr. Malini Raghavan, Department of Microbiology and Immunology, 5641 Medical Science Building II, University of Michigan Medical School, Ann Arbor, MI 48109-0620. E-mail address: malinir{at}umich.edu
3 Abbreviations used in this paper: 
2m, 2-microglobulin; ER, endoplasmic reticulum; HA, hemagglutinin; MOI, multiplicity of infection; Endo-H, endoglycosidase H.
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