ProgramDirirectotor/rP/PrirninccipipaalllnIvnevsetisgtaigtoarto(rLa(Lsat,sFt,irFsti,rsMt,idMdlied)d:leS):hSahasstrtrii , NilJabbhh, , 2 R0O1l AIl 060040-06A1 ABSTRACT deficient mice. the surface of ERAAP-deficient cells. that mediates the trimming of antigenic precursors in the ER is called ERAAP, ft deficient mice. results in vigorous reciprocal immune responses in wild-type versus ERAAP- the surface of ERAAP-deficient cells. The loss and gain of unique pMHC I pMHC I are missing and concomitantly a large set of novel pMHC I emerges on the ER aminopeptidase associated with antigen procesiing.. In ERAAP-deficien results in Vigorous reciprocal immune responses in wild-type versus ERAAP- that mediates the trimming of antigenic precursors in the ER is called ERAAP, fa pMHC I are missing and concomitantly a large set of novel pMHC I emerges on mice. absence of ER trimming disrupts the normal self-pMHC I repertoire. antigen processing continues in the endoplasmic reticulum (ER). antigenic peptide being generated in the cytoplasm, for COB T cells. peptide/MHC class I complexes (pMHC I) on the cell surface as potential ligand mice, absence of ER trimming disrupts the normal self-pMHC I repertoire. Mani antigen processing continues in the endoplasmic reticulum (ER). The protease antigenic peptide being generated in the cytoplasm, recent findings show that for CD8 T cells. Contrary to text book models which often depict the final peptide/MHC class I complexes (pMHC I) on the cell surface as potential ligands immune surveilance. The antigen processing mechanisms yields thousands of The long term goal of our research is to understand and manipulate Contrary to text book models which often depict the final The antigen processing mechanisms yie,lds thousands of The loss and gain of unique pMHC recent findings show that In ERAAP-deficien E The protease I Manv Corn -cu '.. cam cells. processing pathway and immunogenicity. or absence of ERAAP by mass-spectrometry, and (c) the cellular mechanisms used for eliciting COB T cell responses to unique pMHC and origin of the unique immunogenic pMHC I generated in the absence of ERAAP, (b) global analysis of the pMHC I repertoire generated in the presence We anticipate the results to provide a deeper understanding of the antiger Here we propose to fill the gaps in our understanding of (a) the structure how the pathway can be manipulated to regulate I in -0'0 ERAAP deficient cells. We anticipate the results to provide a deeper understanding of the antiger and origin of the unique immunogenic pMHC I generated in the absence of immunogenicity. processing pathway and how the pathway can be manipulated to regulate used for eliciting CD8 T cell responses to unique pMHC I in ERAAP deficient or absence of ERAAP by mass-spectrometry, and (c) the cellular mechanisms ERAAP, (b) global analysis of the pMHC I repertoire generated in the presence Here we propose to fill the gaps in our understacoonding of (a) the structure moo cep (0D Qom.
