HLA-DR polymorphisms influencein vivoresponses to staphylococcal toxic shock syndrome toxin-1 in a transgenic mouse model

HLA ◽  
2016 ◽  
Vol 89 (1) ◽  
pp. 20-28 ◽  
Author(s):  
A. Krogman ◽  
A. Tilahun ◽  
C. S. David ◽  
V. R. Chowdhary ◽  
M. P. Alexander ◽  
...  
1992 ◽  
Vol 176 (6) ◽  
pp. 1779-1784 ◽  
Author(s):  
P Panina-Bordignon ◽  
X T Fu ◽  
A Lanzavecchia ◽  
R W Karr

Staphylococcal toxic shock syndrome toxin 1 (TSST-1) binds to major histocompatibility complex class II molecules, and the toxin-class II complexes induce proliferation of T cells expressing V beta 2 sequences. To define the residues involved in TSST-1 binding, a set of transfectants expressing 21 HLA-DR alpha chain mutants were analyzed for their abilities to bind and present TSST-1 and to present an antigenic peptide. Mutations at DR alpha positions 36 and 39 markedly decreased the ability of the DR7 molecule to bind and present TSST-1 but did not affect the ability to present an antigenic peptide. These data indicate that DR alpha residues 36 and 39, predicted to be located on an outer loop, are important in the formation of the TSST-1 binding site on DR molecules.


1992 ◽  
Vol 38 (9) ◽  
pp. 937-944 ◽  
Author(s):  
Raymond H. See ◽  
Gerald Krystal ◽  
Anthony W. Chow

Staphylococcal toxic shock syndrome toxin-1 (TSST-1) as well as staphylococcal enterotoxin A (SEA) and B (SEB) have recently been shown to bind directly to the class II major histocompatibility antigen, HLA-DR. Whereas others have characterized TSST-1 and SEA binding to HLA-DR on transfected L cells or B lymphoma cell lines, we sought evidence for direct binding of TSST-1 and SEA to HLA-DR on purified human monocytes. A single class of high-affinity receptors was found for both TSST-1 (dissociation constant (Kd) 40 nM, 3.4 × 104 receptors per cell) and SEA (Kd 12 nM, 3.2 × 104 receptors per cell) on normal human monocytes. Affinity cross-linking of 125I-labeled toxins to monocytes revealed the presence of two membrane protein subunits with molecular masses consistent with the α and β chains of human HLA-DR (35 and 28 kDa, respectively). The anti-HLA-DR monoclonal antibody L243, but not L203 or 2.06, inhibited radiolabeled toxin binding to human monocytes and neutralized the mitogenic response of human T lymphocytes to both toxins. However, L243 was consistently more effective in blocking radiolabeled TSST-1 than SEA binding to human monocytes from the same donors, suggesting that TSST-1 and SEA may be binding to overlapping epitopes rather than to the same epitope on HLA-DR. Because TSST-1 and SEB bind to distinct epitopes on HLA-DR and because SEA cross competes with both TSST-1 and SEB on the HLA-DR receptor, we postulate that SEA occupies a binding site within HLA-DR that overlaps both TSST-1 and SEB. Future studies focused on receptor-mediated binding of these toxins to human monocytes and T lymphocytes from normal donors and toxic shock syndrome patients may reveal the underlying anomalies that predispose particular individuals to toxic shock syndrome. Key words: monocytes, staphylococcal toxic shock syndrome toxin-1, receptors, HLA-DR, staphylococcal enterotoxin A.


1996 ◽  
Vol 93 (11) ◽  
pp. 5425-5430 ◽  
Author(s):  
M. F. Hofer ◽  
K. Newell ◽  
R. C. Duke ◽  
P. M. Schlievert ◽  
J. H. Freed ◽  
...  

HLA ◽  
2016 ◽  
Vol 88 (1-2) ◽  
pp. 25-34 ◽  
Author(s):  
Y. H. Sheen ◽  
G. Rajagopalan ◽  
C. M. Snapper ◽  
H. Kita ◽  
C.-I. Wi ◽  
...  

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