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PMID: 18308592 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules.

Immunity ·Vol. 28 ·No. 3 ·2008-03-00 ·Pages 324-34

Dai S, Huseby ES, Rubtsova K, Scott-Browne J, Crawford F, Macdonald WA, Marrack P, Kappler JW

Abstract

To test whether highly crossreactive alphabeta T cell receptors (TCRs) produced during limited negative selection best illustrate evolutionarily conserved interactions between TCR and major histocompatibility complex (MHC) molecules, we solved the structures of three TCRs bound to the same MHC II peptide (IAb-3K). The TCRs had similar affinities for IAb-3K but varied from noncrossreactive to extremely crossreactive with other peptides and MHCs. Crossreactivity correlated with a shrinking, increasingly hydrophobic TCR-ligand interface, involving fewer TCR amino acids. A few CDR1 and CDR2 amino acids dominated the most crossreactive TCR interface with MHC, including Vbeta8 48Y and 54E and Valpha4 29Y, arranged to impose the familiar diagonal orientation of TCR on MHC. These interactions contribute to MHC binding by other TCRs using related V regions, but not usually so dominantly. These data show that crossreactive TCRs can spotlight the evolutionarily conserved features of TCR-MHC interactions and that these interactions impose the diagonal docking of TCRs on MHC.

MeSH Terms
Amino Acid Sequence Animals Antigen Presentation/immunology Conserved Sequence Cross Reactions Histocompatibility Antigens Class II/immunology Humans Lymphocyte Activation/immunology Protein Structure, Quaternary Receptors, Antigen, T-Cell, alpha-beta/chemistry,immunology Surface Plasmon Resonance T-Lymphocytes/immunology
Chemicals
Histocompatibility Antigens Class II Receptors, Antigen, T-Cell, alpha-beta
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Dai Shaodong
Howard Hughes Medical Institute and National Jewish Medical and Research Center, Denver, CO 80206, USA.
Huseby Eric S
Rubtsova Kira
Scott-Browne James
Crawford Frances
Macdonald Whitney A
Marrack Philippa
Kappler John W
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2008.01.008
Published
2008-03-00
Epub
2008-00-28
Pages
324-34
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2287197
Subset
IM
Grants
NIAID NIH HHS · R01 AI018785 · United States
NIAID NIH HHS · R01 AI052225 · United States
NIAID NIH HHS · P01 AI022295-20 · United States
NIAID NIH HHS · AI-17134 · United States
NIAID NIH HHS · R37 AI018785 · United States
Howard Hughes Medical Institute · United States
NIAID NIH HHS · R56 AI017134 · United States
NIAID NIH HHS · R01 AI018785-24 · United States
NIAID NIH HHS · R01 AI052225-05 · United States
NIAID NIH HHS · R56 AI018785 · United States
NIAID NIH HHS · R01 AI018785-25A1 · United States
NIAID NIH HHS · R01 AI018785-23 · United States
NIAID NIH HHS · R01 AI018785-26 · United States
NIAID NIH HHS · AI-18785 · United States
NIAID NIH HHS · R01 AI017134 · United States
NIAID NIH HHS · R01 AI018785-22 · United States
NIAID NIH HHS · P01 AI022295-21A1 · United States
NIAID NIH HHS · AI-22295 · United States
NIAID NIH HHS · P01 AI022295-21A16790 · United States
NIAID NIH HHS · P01 AI022295 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2008.01.008 PMC Full Text View journal details
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