T-cell recognition of Ia molecules selectively altered by a single amino acid substitution

Science ◽  
1986 ◽  
Vol 231 (4735) ◽  
pp. 255-258 ◽  
Author(s):  
M. Brown ◽  
L. Glimcher ◽  
E. Nielsen ◽  
W. Paul ◽  
R. Germain
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Amino Acid Substitution ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
Cell Recognition ◽  
T Cell Recognition

scholarly journals A Single-Amino-Acid Substitution in a Polymerase Protein of an H5N1 Influenza Virus Is Associated with Systemic Infection and Impaired T-Cell Activation in Mice

2009 ◽  
Vol 83 (21) ◽  
pp. 11102-11115 ◽  
Author(s):  
Jamie L. Fornek ◽  
Laura Gillim-Ross ◽  
Celia Santos ◽  
Victoria Carter ◽  
Jerrold M. Ward ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Amino Acid ◽  
T Cell ◽  
Amino Acid Substitution ◽  
Systemic Infection ◽  
Influenza Viruses ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
H5n1 Influenza

ABSTRACT The transmission of H5N1 influenza viruses from birds to humans poses a significant public health threat. A substitution of glutamic acid for lysine at position 627 of the PB2 protein of H5N1 viruses has been identified as a virulence determinant. We utilized the BALB/c mouse model of H5N1 infection to examine how this substitution affects virus-host interactions and leads to systemic infection. Mice infected with H5N1 viruses containing lysine at amino acid 627 in the PB2 protein exhibited an increased severity of lesions in the lung parenchyma and the spleen, increased apoptosis in the lungs, and a decrease in oxygen saturation. Gene expression profiling revealed that T-cell receptor activation was impaired at 2 days postinfection (dpi) in the lungs of mice infected with these viruses. The inflammatory response was highly activated in the lungs of mice infected with these viruses and was sustained at 4 dpi. In the spleen, immune-related processes including NK cell cytotoxicity and antigen presentation were highly activated by 2 dpi. These differences are not attributable solely to differences in viral replication in the lungs but to an inefficient immune response early in infection as well. The timing and magnitude of the immune response to highly pathogenic influenza viruses is critical in determining the outcome of infection. The disruption of these factors by a single-amino-acid substitution in a polymerase protein of an influenza virus is associated with severe disease and correlates with the spread of the virus to extrapulmonary sites.

scholarly journals Pocket 4 of the HLA-DR(α,β 1*0401) molecule is a major determinant of T cells recognition of peptide.

1995 ◽  
Vol 181 (3) ◽  
pp. 915-926 ◽  
Author(s):  
X T Fu ◽  
C P Bono ◽  
S L Woulfe ◽  
C Swearingen ◽  
N L Summers ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Peptide Binding ◽  
Alpha Helix ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
Hla Dr ◽  
Alpha Beta

To investigate the functional roles of individual HLA-DR residues in T cell recognition, transfectants expressing wild-type or mutant DR(alpha,beta 1*0401) molecules with single amino acid substitutions at 14 polymorphic positions of the DR beta 1*0401 chain or 19 positions of the DR alpha chain were used as antigen-presenting cells for five T cell clones specific for the influenza hemagglutinin peptide, HA307-19. Of the six polymorphic positions in the DR beta floor that were examined, mutations at only two positions eliminated T cell recognition: positions 13 (four clones) and 28 (one clone). In contrast, individual mutations at DR beta positions 70, 71, 78, and 86 on the alpha helix eliminated recognition by each of the clones, and mutations at positions 74 and 67 eliminated recognition by four and two clones, respectively. Most of the DR alpha mutations had minimal or no effect on most of the clones, although one clone was very sensitive to changes in the DR alpha chain, with loss of recognition in response to 10 mutants. Mutants that abrogated recognition by all of the clones were assessed for peptide binding, and only the beta 86 mutation drastically decreased peptide binding. Single amino acid substitutions at polymorphic positions in the central part of the DR beta alpha helix disrupted T cell recognition much more frequently than substitutions in the floor, suggesting that DR beta residues on the alpha helix make relatively greater contributions than those in the floor to the ability of the DR(alpha,beta 1*0401) molecule to present HA307-19. The data indicate that DR beta residues 13, 70, 71, 74, and 78, which are located in pocket 4 of the peptide binding site in the crystal structure of the DR1 molecule, exert a major and disproportionate influence on the outcome of T cell recognition, compared with other polymorphic residues.

The response of bovine beta-lactoglobulin-specific T-cell clones to single amino acid substitution of T-cell core epitope

2008 ◽  
Vol 0 (0) ◽  
pp. 080305221334077-??? ◽  
Author(s):  
Masashi Kondo ◽  
Hideo Kaneko ◽  
Toshiyuki Fukao ◽  
Kiyotaka Suzuki ◽  
Heima Sakaguchi ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Amino Acid Substitution ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
T Cell Clones ◽  
Cell Clones ◽  
Beta Lactoglobulin

Conserved V(D)J junctional sequence of cross-reactive cytotoxic T cell receptor idiotype and the effect of a single amino acid substitution

1991 ◽  
Vol 21 (2) ◽  
pp. 483-488 ◽  
Author(s):  
Toshiyasu Hirama ◽  
Sunao Takeshita ◽  
Yuji Matsubayashi ◽  
Michihiro Iwashiro ◽  
Tohru Masuda ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Amino Acid Substitution ◽  
Cell Receptor ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
Cytotoxic T Cell

scholarly journals Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand

Immunity ◽  
1995 ◽  
Vol 2 (4) ◽  
pp. 373-380 ◽  
Author(s):  
Anja Windhagen ◽  
Christian Schooz ◽  
Per Höllsberg ◽  
Hikoaki Fukaura ◽  
Alessandro Sette ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Amino Acid Substitution ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
Peptide Ligand ◽  
T Cell Clones ◽  
Autoreactive T Cell ◽  
Cell Clones

Single amino acid substitution alters T-cell determinant selection during antigen processing of staphylococcal nuclease

Peptides 1990 ◽  
1991 ◽  
pp. 895-897
Author(s):  
John A. Smith ◽  
Zhuoru Liu ◽  
Kevin P. Williams ◽  
Daniel B. Kassel ◽  
Birgit Roellinger ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Amino Acid Substitution ◽  
Antigen Processing ◽  
Staphylococcal Nuclease ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid
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