Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26831112
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26831112
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Proc+Natl+Acad+Sci+U+S+A
2016 ; 113
(11
): 3000-5
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Functional evidence for TCR-intrinsic specificity for MHCII
#MMPMID26831112
Parrish HL
; Deshpande NR
; Vasic J
; Kuhns MS
Proc Natl Acad Sci U S A
2016[Mar]; 113
(11
): 3000-5
PMID26831112
show ga
How T cells become restricted to binding antigenic peptides within class I or
class II major histocompatibility complex molecules (pMHCI or pMHCII,
respectively) via clonotypic T-cell receptors (TCRs) remains debated. During
development, if TCR-pMHC interactions exceed an affinity threshold, a signal is
generated that positively selects the thymocyte to become a mature CD4(+) or
CD8(+) T cell that can recognize foreign peptides within MHCII or MHCI,
respectively. But whether TCRs possess an intrinsic, subthreshold specificity for
MHC that facilitates sampling of the peptides within MHC during positive
selection or T-cell activation is undefined. Here we asked if increasing the
frequency of lymphocyte-specific protein tyrosine kinase (Lck)-associated CD4
molecules in T-cell hybridomas would allow for the detection of subthreshold
TCR-MHC interactions. The reactivity of 10 distinct TCRs was assessed in response
to selecting and nonselecting MHCII bearing cognate, null, or "shaved" peptides
with alanine substitutions at known TCR contact residues: Three of the TCRs were
selected on MHCII and have defined peptide specificity, two were selected on MHCI
and have a known pMHC specificity, and five were generated in vitro without
defined selecting or cognate pMHC. Our central finding is that IL-2 was made when
each TCR interacted with selecting or nonselecting MHCII presenting shaved
peptides. These responses were abrogated by anti-CD4 antibodies and mutagenesis
of CD4. They were also inhibited by anti-MHC antibodies that block TCR-MHCII
interactions. We interpret these data as functional evidence for TCR-intrinsic
specificity for MHCII.
free
free
free
