A Q Region Product as a CTL Restriction Element?

H-2 Antigens ◽  
1987 ◽  
pp. 359-369 ◽  
Author(s):  
Donal B. Murphy ◽  
Robert J. Homer
Keyword(s):  
Region Product ◽  
Restriction Element

scholarly journals Conservation of mucosal associated invariant T (MAIT) cells and the MR1 restriction element in ruminants, and abundance of MAIT cells in spleen

2010 ◽  
Vol 41 (5) ◽  
pp. 62 ◽  
Author(s):  
Nick Goldfinch ◽  
Peter Reinink ◽  
Timothy Connelley ◽  
Ad Koets ◽  
Ivan Morrison ◽  
...  
Keyword(s):  
Mait Cells ◽  
Restriction Element

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
Keyword(s):  
Measles Virus ◽  
Cytotoxic T Lymphocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Cytotoxic T Cell ◽  
Beta Chain ◽  
Cell Clones ◽  
Structural Differences ◽  
D Region ◽  
Restriction Element

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.

scholarly journals Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human-mouse class I major histocompatibility complex.

1991 ◽  
Vol 173 (4) ◽  
pp. 1007-1015 ◽  
Author(s):  
A Vitiello ◽  
D Marchesini ◽  
J Furze ◽  
L A Sherman ◽  
R W Chesnut
Keyword(s):  
Transgenic Mice ◽  
T Lymphocyte ◽  
Matrix Protein ◽  
Cytotoxic T Lymphocyte ◽  
Dominant Role ◽  
Class I ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Restriction Element ◽  
Hla A2.1

Transgenic murine lines have been constructed that express a chimeric class I molecule composed of the alpha 1 and alpha 2 domains of HLA-A2.1 and the alpha 3, transmembrane, and cytoplasmic domains of H-2Kb. Upon immunization with influenza virus, transgenic mice developed a strong A2.1Kb-restricted cytotoxic T lymphocyte (CTL) response specific for the same matrix protein epitope that serves as the dominant A2.1-restricted determinant in the equivalent human response. Fine specificity analysis of CTL clones using truncated peptides revealed strong similarity between the response repertoire of transgenic mice and that previously reported using influenza-specific A2.1-restricted CTL clones from humans. This suggests that even when considering T cell responses by different species, the alpha 1 and alpha 2 domains of the restriction element play a dominant role in determining the CTL specific repertoire. Thus, substituting the alpha 3 domain of A2.1 with a murine counterpart has permitted development of a transgenic strain that should serve as an excellent model system in studies of HLA-restricted responses.

Concerted rate-limiting proton transfer to sulfur with nucleophilic attack at phosphorus — A new proposed mechanism for hydrolytic decomposition of the P=S pesticide, Diazinon, in moderately acidic sulfuric acid media

2007 ◽  
Vol 85 (6) ◽  
pp. 421-431 ◽  
Author(s):  
Doreen Churchill ◽  
Julian M Dust ◽  
Erwin Buncel
Keyword(s):  
Proton Transfer ◽  
Organophosphorus Pesticide ◽  
Nucleophilic Attack ◽  
Acid Media ◽  
Hydronium Ion ◽  
Neutral Aqueous Solution ◽  
Region Product ◽  
Rate Limiting ◽  
Hydrolysis Of ◽  
Acid Region

We report herein the first kinetic study of a P=S containing organophosphorus pesticide, Diazinon (1), in the moderately concentrated acid region. Product analyses (31P NMR) show that reaction occurs only at the P centre. The rate-acidity profile (kobs vs. molarity of H2SO4) appears as a curve in which the initial slight downward trace (molarity = 1 to ca. 5) is followed by sharper upward curve (molarity ca. 5 to 14). Using treatments involving the excess acidity (X) method, the A-1 and A-2 mechanistic possibilities were found to be inoperative over the full acidity range. A novel mechanism is proposed for the higher acidity (X ca. 2–6) region. This mechanism involves proton transfer to P=S from hydronium ion with concomitant proton transfer from water, which effectively delivers hydroxide to the P centre in a variant of the A-SE2 process. A putative A-2 mechanism in this region is supplanted by the proposed A-SE2 variant where the cyclic array results in proton transfer being efficiently coupled with nucleophilic attack involving water. This constitutes the first report of rate-limiting proton transfer at the P=S functionality in acid hydrolysis of this class of organophosphorus neutroxins. A 600 000-fold acceleration in the decomposition of Diazinon is associated with the change of medium from neutral aqueous solution to the most acidic medium studied (X ca. 6). Key words: phosphorothioate ester hydrolysis, acid catalysis, rate-limiting proton transfer at P=S, excess acidity analysis, new A-SE2 variant mechanism.

I-J as a Restriction Element in the Suppressor T Cell System

1985 ◽  
Vol 83 (1) ◽  
pp. 23-40 ◽  
Author(s):  
Martin E. Dorf ◽  
Baruj Benacerraf
Keyword(s):  
T Cell ◽  
Cell System ◽  
Suppressor T Cell ◽  
Restriction Element

scholarly journals Antigen Mining with Iterative Genome Screens Identifies Novel Diagnostics for the Mycobacterium tuberculosis Complex

2006 ◽  
Vol 13 (1) ◽  
pp. 90-97 ◽  
Author(s):  
Katie Ewer ◽  
Paul Cockle ◽  
Steve Gordon ◽  
Huma Mansoor ◽  
Marc Govaerts ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis Complex ◽  
Streptomyces Coelicolor ◽  
Field Studies ◽  
Cross Reactivity ◽  
Tuberculosis Complex ◽  
Research Priority ◽  
Histocompatibility Complex ◽  
Specific Antigens ◽  
Restriction Element ◽  
Definition Of

ABSTRACT The definition of antigens for the diagnosis of human and bovine tuberculosis is a research priority. If diagnosis is to be used alongside Mycobacterium bovis BCG-based vaccination regimens, it will be necessary to have reagents that allow the discrimination of infected and vaccinated animals. A list of 42 potential M. bovis-specific antigens was prepared by comparative analysis of the genomes of M. bovis, M. avium subsp. avium, M. avium subsp. paratuberculosis, and Streptomyces coelicolor. Potential antigens were tested by applying them in a high-throughput peptide-based screening system to M. bovis-infected and BCG-vaccinated cattle and to cattle without prior exposure to M. bovis. A response hierarchy of antigens was established by comparing responses in infected animals. Three antigens (Mb2555, Mb2890, and Mb3895) were selected for further study, as they were strongly recognized in experimentally infected animals but with low or no frequency in BCG-vaccinated and naïve cows. Interestingly, all three antigens were recognized in animals vaccinated against Johne's disease, suggesting the presences of epitopes cross-reacting with M. avium subsp. paratuberculosis antigens. Eight peptides from the three antigens studied in detail were identified as immunodominant and were characterized in terms of major histocompatibility complex class II restriction element usage and shown to be restricted through both DR and DQ molecules. Reasons for antigenic cross-reactivity with M. avium subsp. paratuberculosis and refinement of the in silico strategy to predict such cross-reactivity from the primary protein sequence will be discussed. Evaluation of the peptides identified from the three dominant antigens by use of larger field studies is now a priority.

scholarly journals Recognition of the Major Histocompatibility Complex Restriction Element Modulates CD8+ T Cell Specificity and Compensates for Loss of  T Cell Receptor Contacts with the Specific Peptide

1999 ◽  
Vol 189 (6) ◽  
pp. 883-894 ◽  
Author(s):  
Johan K. Sandberg ◽  
Klas Kärre ◽  
Rickard Glas
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Peptide Ligand ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Cell Specificity ◽  
Restriction Element

Triggering of a T cell requires interaction between its specific receptor (TCR) and a peptide antigen presented by a self–major histocompatibility complex (MHC) molecule. TCR recognition of self-MHC by itself falls below the threshold of detection in most systems due to low affinity. To study this interaction, we have used a read-out system in which antigen-specific effector T cells are confronted with targets expressing high levels of MHC compared with the selecting and priming environment. More specifically, the system is based on CD8+ T cells selected in an environment with subnormal levels of MHC class I in the absence of β2-microglobulin. We observe that the MHC restriction element can trigger viral peptide-specific T cells independently of the peptide ligand, provided there is an increase in self-MHC density. Peptide-independent triggering required at least four times the natural in vivo level of MHC expression. Furthermore, recognition of the restriction element at expression levels below this threshold was still enough to compensate for lack of affinity to peptides carrying alanine substitutions in major TCR contact residues. Thus, the specificity in TCR recognition and T cell activation is fine tuned by the avidity for self-MHC, and TCR avidities for peptide and MHC may substitute for each other. These results demonstrate a functional role for TCR avidity for self-MHC in tuning of T cell specificity, and support a role for cross-reactivity on “self” during T cell selection and activation.

scholarly journals Limiting dilution comparison of the repertoires of high and low responder MHC-restricted T cells.

1988 ◽  
Vol 167 (3) ◽  
pp. 1100-1113 ◽  
Author(s):  
M Kojima ◽  
K B Cease ◽  
G K Buckenmeyer ◽  
J A Berzofsky
Keyword(s):  
T Cells ◽  
Cell Lines ◽  
Sperm Whale ◽  
Cell Repertoire ◽  
Restriction Element ◽  
Low Responder ◽  
Low X ◽  
Limiting Dilution ◽  
Immunodominant Epitopes

To approach the mechanism that determines Ir gene-controlled high or low responsiveness to whole proteins, such as sperm whale myoglobin (SWMb), we compared the repertoires of high and low responder haplotype-restricted T cells for different myoglobin epitopes by limiting dilution frequency analysis. Poisson analysis was performed using long-term limiting dilution cell lines of (B10.BR [low] X B10.D2[high])F1 T cells maintained on high or low responder APCs. The cell lines were tested with SWMb peptides and fragments for T cell repertoire fine specificities and Ia restrictions. The frequency of SWMb-specific F1 T cells responsive on B10.BR (H-2k) APCs was 2.5-3.6-fold lower than on B10.D2 (H-2d) APCs. Strikingly, all of the H-2k-restricted T cells used I-Ek as a restriction element, whereas both I-Ad- and I-Ed-restricted T cells were found among the H-2d-restricted lines. The I-Ad-restricted T cells were dominant, and the majority was specific for the synthetic peptide 102-118. T cells specific for peptide 132-146, dominant in association with I-Ed, were less frequent. However, no detectable H-2k-restricted T cells were specific for either of these peptides, but instead they were specific for fragment 1-55 or peptide 59-80. Fragment 1-55 also stimulated a similar number of H-2d-restricted T cells. Therefore, the low response of F1 T cells on H-2k-presenting cells may be due to the failure to see myoglobin plus I-Ak, in particular the immunodominant site around Glu 109, in contrast to the dominant response of high responder mice (both H-2d and H-2s) focused on the I-A molecule and the site around residue Glu 109. The I-E- low responder B10 strain also failed to respond to peptide 102-118, supporting the idea that the low responder status results from a limited repertoire lacking response to 102-118 plus I-A. In those strains that respond to the immunodominant site 102-118, the frequency of T cells in the repertoire specific for this site was always considerably greater than that for other sites. These results suggest that there is an important difference between immunodominant epitopes and minor epitopes and that Ir gene-controlled low responsiveness to a natural whole protein may be due primarily to the failure to respond to a single immunodominant site, even though a number of other epitopes can be recognized.

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