scholarly journals Identification of a specific HLA DR2 Ia molecule as a restriction element for measles virus-specific HLA class II-restricted cytotoxic T cell clones.

1985 ◽  
Vol 161 (1) ◽  
pp. 263-268 ◽  
Author(s):  
S Jacobson ◽  
G T Nepom ◽  
J R Richert ◽  
W E Biddison ◽  
H F McFarland

By using a panel of HLA-D-defined subtypes of HLA-DR2 HCL with known beta chain structural variabilities, we have demonstrated that HLA-DR2, OKT4+ cytotoxic T lymphocyte (CTL) clones specific for measles virus are apparently restricted to a distinct DR beta chain. The presence of this DR beta 2 molecule correlated precisely with the susceptibility of measles virus-infected HLA-DR2 HCL to lysis by these CTL clones. These studies demonstrate that delineation of HLA-DR2 into various subgroups can have a functional significance that parallels the structural differences within the HLA-D region. These results are discussed in the context of the possible association of HLA class II-restricted, measles virus-specific CTL and multiple sclerosis.

1985 ◽  
Vol 161 (6) ◽  
pp. 1569-1574 ◽  
Author(s):  
G Paulsen ◽  
E Qvigstad ◽  
G Gaudernack ◽  
L Rask ◽  
R Winchester ◽  
...  

Two T4 cell clones (TLC) specific for antigenic epitopes on Chlamydia trachomatis were studied. Using a panel of allogeneic antigen-presenting cells (APC), both TLC were found to be restricted by HLA class II elements closely associated with, but not identical to the DRw5S specificity, as determined by highly selected alloantisera, a monoclonal antibody (mAb), 109d6, and confirmed on the DNA level by determination of restriction fragment length polymorphisms (RFLP) with a DR beta probe. Furthermore, HLA-DR-specific mAb, including 109d6, but not other HLA class II- or class I-specific antibodies inhibited the two TLC, strongly suggesting that the restriction element is expressed by a DR molecule. Using digestion with Hind III restriction enzyme and a DR beta probe, we found a complete concordance between the appearance of a 9.3 kilobase band and the ability of allogeneic APC to restimulate the T cell clones. Thus, the restriction element for these T cell clones appear to be expressed by DR molecules, but can, at present, only be detected at the genomic level.


1990 ◽  
Vol 171 (6) ◽  
pp. 2011-2024 ◽  
Author(s):  
T H Ottenhoff ◽  
T Mutis

Mycobacterial antigens not only stimulate Th cells that produce macrophage-activating factors, but also CD4+ and CD8+ CTL that lyse human macrophages. The mycobacterial recombinant 65-kD hsp was previously found to be an important target antigen for polyclonal CD4+ CTL. Because of the major role of 65-kD hsp in the immune response to mycobacterial as well as autoantigens, we have studied CTL activity to this protein at the clonal level. HLA-DR or HLA-DQ restricted, CD4+CD8- T cell clones that recognize different peptides of the M. leprae 65-kD hsp strongly lysed EBV-BLCL pulsed with specific but not irrelevant peptide. No bystander lysis of B cells, T cells, or tumor cells was seen. Target cell lysis could not be triggered by PMA + Ca2+ ionophore alone and depended on active metabolism. Interestingly, these CD4+ CTL also strongly lysed themselves and other HLA-class II compatible CD4+ (TCR-alpha/beta or -gamma/delta) or CD8+ CTL clones in the presence of peptide, suggesting that CTL are not actively protected from CTL-mediated lysis. Cold target competition experiments suggested that EBV-BLCL targets were more efficiently recognized than CD4+ CTL targets. These results demonstrate that hsp65 peptide-specific HLA class II-restricted CD4+ T cell clones display strong peptide-dependent cytolytic activity towards both APCs, and, unexpectedly, CD4+ and CD8+ CTL clones, including themselves. Since, in contrast to murine T cells human T cells express class II, CTL-mediated T cell killing may represent a novel immunoregulatory pathway in man.


1988 ◽  
Vol 85 (4) ◽  
pp. 1209-1212 ◽  
Author(s):  
R. P. Sekaly ◽  
S. Jacobson ◽  
J. R. Richert ◽  
C. Tonnelle ◽  
H. F. McFarland ◽  
...  

1984 ◽  
pp. 495-499 ◽  
Author(s):  
N. Flomenberg ◽  
K. Horibe ◽  
R. W. Knowles ◽  
D. Williams ◽  
K. Rosenkrantz ◽  
...  

1994 ◽  
Vol 169 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Anthony N. Warrens ◽  
Tricia Heaton ◽  
Sid Sidhu ◽  
Giovanna Lombardi ◽  
Robert I. Lechler

1986 ◽  
Vol 163 (5) ◽  
pp. 1314-1318 ◽  
Author(s):  
M Zauderer ◽  
A Iwamoto ◽  
T W Mak

gamma gene rearrangements similar to those described for cytotoxic T cell lines are found in L3T4+, autoreactive, or KLH-specific cloned helper T cell lines. High levels of gamma RNA transcripts were, in addition, detected in four out of five L3T4+, class II MHC-specific, autoreactive T cell clones, and in at least one of three KLH-specific, class II MHC-restricted clones. This contrasts with previously reported (9) expression of gamma RNA in only 1 of 11 antigen-specific helper T cell lines.


1985 ◽  
Vol 6 (3) ◽  
pp. 89-94 ◽  
Author(s):  
Fritz H. Bach
Keyword(s):  
Class Ii ◽  

2005 ◽  
Vol 56 (11) ◽  
pp. 798-807 ◽  
Author(s):  
Inna G. Ovsyannikova ◽  
Robert M. Jacobson ◽  
Jenna E. Ryan ◽  
Robert A. Vierkant ◽  
V. Shane Pankratz ◽  
...  

1999 ◽  
Vol 189 (5) ◽  
pp. 767-778 ◽  
Author(s):  
Pascal Chaux ◽  
Valérie Vantomme ◽  
Vincent Stroobant ◽  
Kris Thielemans ◽  
Jurgen Corthals ◽  
...  

MAGE-type genes are expressed by many tumors of different histological types and not by normal cells, except for male germline cells, which do not express major histocompatibility complex (MHC) molecules. Therefore, the antigens encoded by MAGE-type genes are strictly tumor specific and common to many tumors. We describe here the identification of the first MAGE-encoded epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules to CD4+ T lymphocytes. Monocyte-derived dendritic cells were loaded with a MAGE-3 recombinant protein and used to stimulate autologous CD4+ T cells. We isolated CD4+ T cell clones that recognized two different MAGE-3 epitopes, MAGE-3114–127 and MAGE-3121–134, both presented by the HLA-DR13 molecule, which is expressed in 20% of Caucasians. The second epitope is also encoded by MAGE-1, -2, and -6. Our procedure should be applicable to other proteins for the identification of new tumor-specific antigens presented by HLA class II molecules. The knowledge of such antigens will be useful for evaluation of the immune response of cancer patients immunized with proteins or with recombinant viruses carrying entire genes coding for tumor antigens. The use of antigenic peptides presented by class II in addition to peptides presented by class I may also improve the efficacy of therapeutic antitumor vaccination.


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