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Ma X , Serna A , Xu RH , Sigal LJ
The amino acid sequences flanking an antigenic determinant can strongly affect MHC class I cross-presentation without altering direct presentation
J Immunol. 2009 Apr 15;182(8) :4601-7
PMID: 19342634    PMCID: PMC2756161   
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Abstract
Direct presentation (DP) and cross presentation (CP) on MHC I by professional APCs are defined by the internal or external source of the Ag, respectively. Although some Ags are substrates for both DP and CP, others are only substrates for DP. The reasons for this difference remain largely unknown. In this study, we studied in tissue culture and also in vivo, the effects of altering the length and sequence of the amino acid chains flanking an MHC class I restricted determinant (the chicken OVA OVA(258-265), SIINFEKL) that is normally a good substrate for both DP and CP. We demonstrate that CP but not DP strictly requires flanking N and C-terminal extensions of minimal length. Furthermore, we show that removal but not replacement of just one amino acid 22 residues downstream from the determinant is sufficient to strongly affect CP without affecting either protein stability or DP. Thus, our work shows that the flanking residues of an antigenic determinant can differentially affect CP and DP, and that features of the Ag other than half-life can have a major impact in CP. Our studies may have implications for understanding CP in viral infections and possibly for the design of new vaccines.
Notes
Ma, Xueying Serna, Amparo Xu, Ren-Huan Sigal, Luis J CA006927/CA/NCI NIH HHS/United States R01AI048849/AI/NIAID NIH HHS/United States R21AI058179/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural United States Journal of immunology (Baltimore, Md. : 1950) J Immunol. 2009 Apr 15;182(8):4601-7.