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Cluster of Differenciation(CD) replacement... Immunology

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Cluster of Differenciation(CD) replacement... Immunology

Postby mortonman1 » Thu May 27, 2010 3:21 am

Hi, i was wondering if it's possible to use radiation or some process in order to change the surface proteins, CD's, on T-cells. I was particularly thinking of replacing the CD protein from a gamma/delta T-cell, which they are still researching, and putting it on a Cd4 T-cell. Is this possible? If so how would i do it?
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Postby biohazard » Thu May 27, 2010 7:43 am

You can use radioation only to induce random mutations, and usually to get your desired mutation you cause a thousand non-wanted mutations as a side product.

What CD protein you specifically want to replace? There are dozens of them. Or do you mean replacing the normal alpha/beta T cell receptor with the more rare gamma/delta chains?

In mice you can produce knock-out or genetically engineered T cells, but that is an extremely laborous and costly process.

In theory, you could deliver the gamma/delta genes to a normal alpha/beta CD4+ T cell with a retroviral vector and maybe even silence the alpha/beta genes with siRNA or similar.

For more simple gamma/delta receptor studies you can genetically engineer immortalized T cells (such as Jurkat cells) by transferring the desired genes and then screening for gamma/delta positive cells and cloning them for further studies. That's what we have done in our lab recently.
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Postby mortonman1 » Thu May 27, 2010 10:24 pm

Ok you answered everything pretty much. but I'm more so wondering if one can move the CD3 protein from a gamma t cell to a Cd4 t cell, and place the CD3 protein on the surface of the CD4 t cell to act as a replacement. This would hopefully make it so that HIV gp120 wouldnt be able to bind to t-cells
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Re:

Postby biohazard » Fri May 28, 2010 12:39 pm

mortonman1 wrote:Ok you answered everything pretty much. but I'm more so wondering if one can move the CD3 protein from a gamma t cell to a Cd4 t cell, and place the CD3 protein on the surface of the CD4 t cell to act as a replacement. This would hopefully make it so that HIV gp120 wouldnt be able to bind to t-cells


Perhaps I'm missing something here, but as far as I know both gamma/delta and "normal" alpha/beta T cells express CD3, so by transferring the CD3 from an A/B cell to a G/D cell makes no difference. Furthermore, I believe both these T cells express CD4 and are suspectible to HIV infection.

Finally, I don't hitnk you can replace CD3 with CD4 or the other way round without losing the functionality of the cell: lack of CD3 makes the T cell receptor non-functional (a prerequisite for many of the fundamental functions of T cells) and lack of CD4 makes A/B T cells non-responsive for antigens offered by antigen-presented cells via their MHC II molecules. It is suggested, though, that G/D cells may function without MHC-recognition, but they may still need CD4 for other functions.
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Postby mortonman1 » Sat May 29, 2010 4:22 am

Well I am in high school, and really have no idea what i'm talking about, but im really interested in immunology. so if im wrong, i guess i am. you said that both a/b and d/g t-cells present CD3? i thought that d/g t cells presented CD3 and a/b presented CD4?
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Postby biohazard » Mon May 31, 2010 6:10 am

The alpha/beta and gamma/delta designations come from the type of chains that form the T cell receptor (TCR). Majority of the T cells have alpha and beta chains in their TCR. CD3 is the co-receptor of the TCR, and thus both a/b and g/d T cells have CD3 expressed with the TCR - without CD3 the TCR is dysfunctional.

CD4 is the co-receptor of TCR that is involved in the recognition of antigens on the surface of the antigen presenting cells (APCs). They are involved in MHC II:peptide recognition, where the peptide is a piece of an antigen the APC has fagosytosed and is displaying to T helper cells (CD4 T cells). Furthermore, this is the target molecule of HIV, just as you mentioned. CD4 is present also in monocytes and macrophages.

The other big subpopulation of T cells is CD8 cells, which in turn recognize MHC I-bound antigens displayed on the surface of body's own cells. Thus they can for example recognize virus infected cells and kill them. Thus they are called cytotoxic T cells, because they are "toxic" to infected cells.

However, the function of g/d T cells is not very well known, and it is possible that they can be actvated without the MHC:peptide recognition involving CD4. That still does not mean that we could replace all our a/b CD4 T helper cells with g/d cells that lack CD4, because a/b CD4 T cells are one of the most crucial components of the adaptive immune system.
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Postby becky34 » Mon Aug 01, 2011 7:55 am

CD stands for cluster of differentiation, which indicates a defined subset of cellular surface receptors (epitopes) that identify cell type and stage of differentiation, and which are recognized by antibodies.

There are more than 250 identified clusters, each a different molecule, coating the surface of B lymphocytes and T lymphocytes.
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