2v2w: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
All thymically selected T cells are inherently cross-reactive, yet many | All thymically selected T cells are inherently cross-reactive, yet many data indicate a fine specificity in antigen recognition, which enables virus escape from immune control by mutation in infections such as the human immunodeficiency virus (HIV). To address this paradox, we analyzed the fine specificity of T cells recognizing a human histocompatibility leukocyte antigen (HLA)-A2-restricted, strongly immunodominant, HIV gag epitope (SLFNTVATL). The majority of 171 variant peptides tested bound HLA-A2, but only one third were recognized. Surprisingly, one recognized variant (SLYNTVATL) showed marked differences in structure when bound to HLA-A2. T cell receptor (TCR) recognition of variants of these two peptides implied that they adopted the same conformation in the TCR-peptide-major histocompatibility complex (MHC) complex. However, the on-rate kinetics of TCR binding were identical, implying that conformational changes at the TCR-peptide-MHC binding interface occur after an initial permissive antigen contact. These findings have implications for the rational design of vaccines targeting viruses with unstable genomes. | ||
==Disease== | |||
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Ankylosing spondylitis, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Hypoproteinemia, hypercatabolic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109700 109700]], Stevens-Johnson syndrome, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]] | |||
==About this Structure== | ==About this Structure== | ||
2V2W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure | 2V2W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 2BSU. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V2W OCA]. | ||
==Reference== | ==Reference== | ||
| Line 15: | Line 18: | ||
[[Category: Dong, T.]] | [[Category: Dong, T.]] | ||
[[Category: Dorrell, L.]] | [[Category: Dorrell, L.]] | ||
[[Category: Douek, D | [[Category: Douek, D C.]] | ||
[[Category: Gleria, K | [[Category: Gleria, K Di.]] | ||
[[Category: Harlos, K.]] | [[Category: Harlos, K.]] | ||
[[Category: Jones, E | [[Category: Jones, E Y.]] | ||
[[Category: Lee, J | [[Category: Lee, J K.]] | ||
[[Category: Mcmichael, A | [[Category: Mcmichael, A J.]] | ||
[[Category: Merwe, P | [[Category: Merwe, P A.Van Der.]] | ||
[[Category: Stewart-Jones, G.]] | [[Category: Stewart-Jones, G.]] | ||
[[Category: aids]] | [[Category: aids]] | ||
| Line 43: | Line 46: | ||
[[Category: ubl conjugation]] | [[Category: ubl conjugation]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:52:50 2008'' | ||
Revision as of 19:52, 21 February 2008
|
T CELL CROSS-REACTIVITY AND CONFORMATIONAL CHANGES DURING TCR ENGAGEMENT
OverviewOverview
All thymically selected T cells are inherently cross-reactive, yet many data indicate a fine specificity in antigen recognition, which enables virus escape from immune control by mutation in infections such as the human immunodeficiency virus (HIV). To address this paradox, we analyzed the fine specificity of T cells recognizing a human histocompatibility leukocyte antigen (HLA)-A2-restricted, strongly immunodominant, HIV gag epitope (SLFNTVATL). The majority of 171 variant peptides tested bound HLA-A2, but only one third were recognized. Surprisingly, one recognized variant (SLYNTVATL) showed marked differences in structure when bound to HLA-A2. T cell receptor (TCR) recognition of variants of these two peptides implied that they adopted the same conformation in the TCR-peptide-major histocompatibility complex (MHC) complex. However, the on-rate kinetics of TCR binding were identical, implying that conformational changes at the TCR-peptide-MHC binding interface occur after an initial permissive antigen contact. These findings have implications for the rational design of vaccines targeting viruses with unstable genomes.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Hypoproteinemia, hypercatabolic OMIM:[109700], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]
About this StructureAbout this Structure
2V2W is a Protein complex structure of sequences from Homo sapiens. This structure supersedes the now removed PDB entry 2BSU. Full crystallographic information is available from OCA.
ReferenceReference
T cell cross-reactivity and conformational changes during TCR engagement., Lee JK, Stewart-Jones G, Dong T, Harlos K, Di Gleria K, Dorrell L, Douek DC, van der Merwe PA, Jones EY, McMichael AJ, J Exp Med. 2004 Dec 6;200(11):1455-66. PMID:15583017
Page seeded by OCA on Thu Feb 21 18:52:50 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Protein complex
- Dong, T.
- Dorrell, L.
- Douek, D C.
- Gleria, K Di.
- Harlos, K.
- Jones, E Y.
- Lee, J K.
- Mcmichael, A J.
- Merwe, P A.Van Der.
- Stewart-Jones, G.
- Aids
- Complex (antigen-peptide)
- Complex (antigen/peptide)
- Disease mutation
- Glycoprotein
- Hiv
- Hla-a2
- Host-virus interaction
- Immune response
- Immune system
- Immunoglobulin domain
- Membrane
- Mhc
- Mhc i
- Polymorphism
- Pyrrolidone carboxylic acid
- Tcr
- Transmembrane
- Ubl conjugation