2hjl: Difference between revisions
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==Overview== | ==Overview== | ||
HLA-B*57 is associated with slower disease progression to AIDS, and CD8+ T, cell responses to B*57-restricted epitopes are thought to contribute to, this protective effect. In this study, we evaluate the B*57-restricted p24, KAFSPEVIPMF (KF11) immune response which is immunodominant during chronic, infection. Previously, we observed that the KF11 clade variants, KGFNPEVIPMF [A2G,S4N] and KAFNPEIIMPF [S4N,V7I], sharing a position 4, mutation, are differentially recognized by KF11-specific T cells. By, combining structural and cellular studies, we now demonstrate that the, KF11 and [A2G,S4N] epitopes induce distinct functional responses in, [A2G,S4N] and KF11-specific T cells, respectively, despite minimal, structural differences between the individual B*57-peptide complexes., Recently, we also elucidated the highly distinct structure of KF11 in, complex with B*5703, and have now characterized the CD8+ T cell repertoire, recognizing this epitope. We now report striking features of TCR, conservation both in terms of TCR Valpha and Vbeta chain usage, and, throughout the hypervariable region. Collectively, our findings highlight, unusual features of the B*5701/B*5703-KF11-specific immune responses which, could influence disease progression and that might be important to, consider when designing future vaccine regimens. | HLA-B*57 is associated with slower disease progression to AIDS, and CD8+ T, cell responses to B*57-restricted epitopes are thought to contribute to, this protective effect. In this study, we evaluate the B*57-restricted p24, KAFSPEVIPMF (KF11) immune response which is immunodominant during chronic, infection. Previously, we observed that the KF11 clade variants, KGFNPEVIPMF [A2G,S4N] and KAFNPEIIMPF [S4N,V7I], sharing a position 4, mutation, are differentially recognized by KF11-specific T cells. By, combining structural and cellular studies, we now demonstrate that the, KF11 and [A2G,S4N] epitopes induce distinct functional responses in, [A2G,S4N] and KF11-specific T cells, respectively, despite minimal, structural differences between the individual B*57-peptide complexes., Recently, we also elucidated the highly distinct structure of KF11 in, complex with B*5703, and have now characterized the CD8+ T cell repertoire, recognizing this epitope. We now report striking features of TCR, conservation both in terms of TCR Valpha and Vbeta chain usage, and, throughout the hypervariable region. Collectively, our findings highlight, unusual features of the B*5701/B*5703-KF11-specific immune responses which, could influence disease progression and that might be important to, consider when designing future vaccine regimens. | ||
==Disease== | |||
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]], Hypoproteinemia, hypercatabolic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109700 109700]], Spondyloarthropathy, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: hla]] | [[Category: hla]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:33:21 2007'' | ||
Revision as of 23:26, 12 November 2007
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Crystal Structure of HLA-B5703 and HIV-1 peptide
OverviewOverview
HLA-B*57 is associated with slower disease progression to AIDS, and CD8+ T, cell responses to B*57-restricted epitopes are thought to contribute to, this protective effect. In this study, we evaluate the B*57-restricted p24, KAFSPEVIPMF (KF11) immune response which is immunodominant during chronic, infection. Previously, we observed that the KF11 clade variants, KGFNPEVIPMF [A2G,S4N] and KAFNPEIIMPF [S4N,V7I], sharing a position 4, mutation, are differentially recognized by KF11-specific T cells. By, combining structural and cellular studies, we now demonstrate that the, KF11 and [A2G,S4N] epitopes induce distinct functional responses in, [A2G,S4N] and KF11-specific T cells, respectively, despite minimal, structural differences between the individual B*57-peptide complexes., Recently, we also elucidated the highly distinct structure of KF11 in, complex with B*5703, and have now characterized the CD8+ T cell repertoire, recognizing this epitope. We now report striking features of TCR, conservation both in terms of TCR Valpha and Vbeta chain usage, and, throughout the hypervariable region. Collectively, our findings highlight, unusual features of the B*5701/B*5703-KF11-specific immune responses which, could influence disease progression and that might be important to, consider when designing future vaccine regimens.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]
About this StructureAbout this Structure
2HJL is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Strong TCR conservation and altered T cell cross-reactivity characterize a B*57-restricted immune response in HIV-1 infection., Gillespie GM, Stewart-Jones G, Rengasamy J, Beattie T, Bwayo JJ, Plummer FA, Kaul R, McMichael AJ, Easterbrook P, Dong T, Jones EY, Rowland-Jones SL, J Immunol. 2006 Sep 15;177(6):3893-902. PMID:16951352
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