Maybe I am missing something but Klebsiella is a bacteria. It does not have HLA or any antigen presenting molecules. What would a bacterium do with HLA or MHC? It is a single cell organism, there are no immune cells to present to.

Please clarify if I misunderstood the question.

Or maybe this is an April Fool's prank?

Actually Mr. Luis, Klebsiella microbes possess various antigens which show molecular similarity and immunological cross-reactivity with HLA-B27, which is main cause of arthritis, so my question was can we amplify those antigens in klebsiella which shows similarity to HLA, and how. Thanks

Dear Saurabh, cross reactivity of mAbs specific to cell surface proteins of mammals with different antigenic determinants of microbial pathogens is ordinary event. Unlikely you will see any sequence similarity between HLA and microbial proteins. To identify microbial antigens reacting with mAbs, you will need to isolate them and to perform sequencing. After this, you will be able to construct primers for subsequent amplification and sequencing of encoding microbial DNA and, then, cloning and identification of genes.

Hello Dmitry, As the literature shows that nitrogen reductase enzyme of klebsiella have sequence similartity to HLA B2705, so can i amplify nitrogen reductase enzyme of klebsiella with Primers specific to HLA B2705, i mean is there any chance that it will get amplify

One aminoacid residue can be encoded by different triplets. Therefore, sequence homology observed on the level of protein will not be necessary accompanied by homology on DNA level. So, you will need to get and analyze the DNA sequences to check for identity and construction of primers. In any case you will need to perform sequencing of amplified product to ensure that your primers work specifically.

I agree with comments given by our colleagues. In the literature there are many papers that reported a sequence similarity between some infectious agents (as bacteria, virus, etc…) with HLA genes, HLA-B51. HLA-B27..etc. That could explain in somewhere how molecular mimicry could induce the development of the some diseases especially the auto-immune diseases. But here, the sequence similarity with HLA gene does not mean that the pathogen expresses HLA molecule. This is only very short sequence which code for one peptide.

Hi Saurabh,

I see your point now.

I agree with Dmitry and Khalid. Don't overinterpret the term 'sequence homology'. In this case there one specific epitope found on the alpha helix of the alpha 1 domain of HLA-B27 (B*27:05, specifically) that seems to be shared with Klebsiella nitrogen reductase. I am sure if you were to do an amino acid alignment, you would find little more homology given the very different functions that these two proteins perform. Thus, the majority of the primers used to identify HLA genes would be useless in amplifying the nitrogen reductase gene. Best to find the gene sequence to Klebsiella NR and design your own set of primers or search for a commercially available set.

Thanks every body...............

I think the best way if you want to see the homology between HLA B27 and Klebsiella proteins is to look at the cross reactive antigens after purifying them and reacting them with anti-HLA B27 antibodies. Then you can analyze these proteins (known or unknown)by various methods. These Klebsiella proteins are not HLA proteins but they mimic these proteins

Personally, I think it is unlikely that comparing peptide epitopes from an alpha helical loop of Klebsiella's nitrogen reductase to HLA B27 will yield much relevant information about the role of bacteria in arthritis. Some arthritis types are definitely sequelae of infections, which has been known since the 1980s. Antigenic cross-reactivity has been recognized since the 1950s (e.g. Forssman antigens). The facts these epitopes cross-react could be the result of molecular mimicry, but it might merely be chance. For it to be molecular mimicry, I'd think the enzyme would have to aid the organism evading the immune response, but I've seen no evidence of this on this forum and therefore I couldn't say whether it contributes to this at all (see below).

While I don't know anything about this enzyme (other than what I've read here), I think Klebsiella nitrogen reductase is probably an internal enzyme in the cell and thus unlikely to be of great antigenic importance when the organism is engulfed and processed for antigen presentation by an antigen presenting cell. However, if it was exported and also an immunodominant epitope or a major product of the bacteria when growing on the host, then I think it could be of greater importance immunologically. Joseph P Caruso, PhD

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I think studying the behavior of the antibody at different times, would be the best way to standardize a functional role of these epitopes

I agree with Dmitry, Khalid and Luis. From a clinical stand point when you address molecular mimicry you should be addressing functional molecular mimicry wherein said protein (nitrogen reductase enzyme of Klebsiella) comprise at least one epitope region which recognises common to a protein in man and elicits an immune response in man which results in protection from infection or autoimmunity as an outcome. Immune responses to mimiced epitopes on pathogens frequently have no effect on pathogen or host. The epitope is not located at a site in man which can be targeted thus no pathology. As stated above by my co contributors molecular mimicry is common in nature and without clinical consequence. For example see the two attached manuscripts (two responses as one answer will only load one attachment).

In addition to what I have stated above molecular mimicry may be a contributing factor to some auto-immune pathology. I would be very interested in seeing a publication from you and your associates which establish a cause and effect whereas mimicry between nitrogen reductase enzyme of Klebsiella and HLA B27:05 resulted in a clinically significant auto immune response in man whereas epitope specific anti B27:05 is responsible for the pathology.

Nice post. Just one thing. Phagocytes, particularly neutrophils, secrete the products of their digestion, thus exposing intracelular antigens to B-cells. Thereby, the likehood of having a pathology through molecular mimicry could be greater than one might think and something the immune system has to deal with.

Hi Pedro, I agree with your thoughts on the occurrence of anti-self antibody to processed self antigen however, in my experience they rarely if ever result in pathology. Such epitopes include:

1. Antigen distribution is restricted to sequestered and/or unavailable locations to the antibody.

3. Epitope location within the host is not available for immune targeting without damage to tissue.

4. Antigen distribution on host cell is at a density lower than required to produce injury but favorable on the desired target resulting in selective targeting.

5. The epitope must not be present in body fluids at concentrations which would neutralize antibody and prevent targeting.

I believe this lack of damage to host tissue by immune responses to mimiced epitopes can be taken advantage of in certain infectious diseases when designing vaccines to mimice epitopes as a treatment or preventative for infection. Please see the USA patents below as I would like your thoughts on this issue. One can be viewed on Research Gate.

3 6,670,181 Full-Text Compositions and methods for treating viral infections

4 6,335,017 Full-Text Compositions and methods for treating viral infections

5 6,258,599 Full-Text Compositions and methods for treating viral infections

6 6,043,347 Full-Text Compositions and methods for treating viral infections

Dear Frank,

I also agree with. Moreover, we do not see pathology because the immune system deal with, suppress if you wish, the generation of self reactive auto-antibodies. CD4 T cells, particularly Tregs, surely play an important role controlling unwanted responses such as those resulting from molecular mimicry and epitope spreading. If T cell tolerance is lost, anything can happen.