SARS E2-spike Protein Mimicking T-cell Receptor Alpha Beta V Chain Proteins?
May 21, 2003
Hello, Steve
As you know, I have been examining the SARS coronavirus E2-spike protein in some detail.
Interestingly, the E2-spike protein appears to be mimicking T-cell Receptor alpha-beta V chain protein (TCRalpha-betaV) in a region about residue 680 to residue 1050 as indexed in the SARS E2-spike protein. The implications of the molecular mimickry of SARS E2-spike protein (which appears to be using a CD13 pathway to enter cells) is that SARS coronavirus will initiate a profound hyperimmune disorder (autoimmune disorder) in some individuals. Individuals who are more likely to have this autoimmune reaction appears to be people of MHC Class II HLA-DR, -DP, and -DQ histocompatibility.
It appears likely that SARS E2-spike protein's mimickry of TCRalpha-betaV is causing an infected person's immune system to respond to the SARS coronavirus as if the virus proteins are, what are called in by the molecular biologists/virologists, a "super antigen." This "super antigen" (mimicking TCRalphabetaV) appears to be deregulating the infected person's own natural T-cell functioning resulting in, what appears very like, a "graft-vs-host" disease in the infected person. The infected person's immune system seems to be responding to the SARS-coronavirus-mimickry of a foreign (not self) histocompatibility complex.
These mimicked T-cell Receptor alpha-beta V chain-like amino acids in SARS coronavirus E2-spike protein appear to be tricking the infected person's immune system into thinking that a foreign histocompatibility complex is present and so the their immune system is activated. As their immune system may be activated and more of their own cells may be displaying CD13 antigen on cell surfaces, the result would be greater opportunity for the virus to spread (as it appears to target CD13 antigen). The more cells that can be invaded, the greater the degree of virus-induced graft-vs-host disease.
In short, what appears to be going on in SARS infection is a virus-induced autoimmune disorder and the body's normal immunological processes are short-circuited. Persons who are killed by the SARS coronavirus are, apparently, having a profound immunological reaction to the molecular mimickry in SARS E2-spike protein which results in a highly active immune system which gives opportunity for the virus to spread even faster. I have explained this reaction most simply this way: SARS E2-spike protein mimickry of T-cell Receptor alpha-beta V chain protein is similar to throwing gasoline on an open fire... think of SARS E2-spike mimickry of T-cell Receptor alpha beta V chain as an immune system "accelerant." If the reader is a molecular biologist, please check the literature on super antigens and their relationship to TCRalphabetaV and the relationship of this to MHC Class II HLA-DR and relationship to autoimmune disease and then examine SARS E2-spike protein amino acids between 700 to 1050 and compare these amino acids to protein 1BWMA at PubMed Central. I have provided technical detail below to any scientist with interest.
More work needs to be done, of course, to understand this virus. Others will need to confirm these observations.
I am providing technical information below.
Thanks, Steve!
Bob Lee
-- multiple sequence alignment below here --
Steve, if you post this, please try to conserve the alignment below in your html posting so to retain the information in the posting. If the posting loses the alignment, then the information is lost to the reader. Thanks.
Note: this information is copyright 2003 (c) Robert E. Lee
Note: this information is granted by Robert E. Lee for display on Steve Quayle's website at http://www.stevequayle.com
Note: copy of this material is granted by Robert E. Lee with the stipulation that ALL material herein be contained including both the Lee 2003 copyright and the Steve Quayle website address at http://www.stevequayle.com
Note: Any written reference concerning SARS E2-spike protein mimicking T-cell Receptor alpha-beta V shall give credit to this original work.
Note: This information was submitted 5/21/2003. As of this date no one anywhere in the world has published on this finding to my knowledge.
gi|29836496|ref|NP_828851.1| PIGAGICASYHTVSLLRSTSQKSIVAYTMSLGADSSIAYSNNTIAIPTNF 700
gi|30173397|sp|P59594|VGL2_CVH PIGAGICASYHTVSLLRSTSQKSIVAYTMSLGADSSIAYSNNTIAIPTNF 700
gi|30023954|gb|AAP13567.1| PIGAGICASYHTVSLLRSTSQKSIVAYTMSLGADSSIAYSNNTIAIPTNF 700
gi|5821923|pdb|1BWM|A ------------------------------------------AVTQSPRN 8
::: ...
gi|29836496|ref|NP_828851.1| SISITTEVMPVSMAKTSVDCNMYICGDSTECANLLLQYGSFCTQLNRALS 750
gi|30173397|sp|P59594|VGL2_CVH SISITTEVMPVSMAKTSVDCNMYICGDSTECANLLLQYGSFCTQLNRALS 750
gi|30023954|gb|AAP13567.1| SISITTEVMPVSMAKTSVDCNMYICGDSTECANLLLQYGSFCTQLNRALS 750
gi|5821923|pdb|1BWM|A KVAVTGGKVTLSCNQTNNHNNMYWYRQDTGHGLRLIHYS----------Y 48
.:::* :.:* :*. . *** :.* . *::*.
gi|29836496|ref|NP_828851.1| GIAAEQDRNTREVFAQVKQMYKTPTLKYFGGFNFSQILPDPLKPTKRSFI 800
gi|30173397|sp|P59594|VGL2_CVH GIAAEQDRNTREVFAQVKQMYKTPTLKYFGGFNFSQILPDPLKPTKRSFI 800
gi|30023954|gb|AAP13567.1| GIAAEQDRNTREVFAQVKQMYKTPTLKYFGGFNFSQILPDPLKPTKRSFI 800
gi|5821923|pdb|1BWM|A GAGSTEK-------GDIPDGYKAS------------------RPSQENFS 73
* .: :. .:: : **:. :*::..*
gi|29836496|ref|NP_828851.1| EDLLFNKVTLADAGFMKQYGECLGDINARDLICAQKFNGLTVLPPLLTDD 850
gi|30173397|sp|P59594|VGL2_CVH EDLLFNKVTLADAGFMKQYGECLGDINARDLICAQKFNGLTVLPPLLTDD 850
gi|30023954|gb|AAP13567.1| EDLLFNKVTLADAGFMKQYGECLGDINARDLICAQKFNGLTVLPPLLTDD 850
gi|5821923|pdb|1BWM|A LILELATPSQTSVYFCASGGQGR----------AEQFFGPGTRLTVLGSD 113
* : . : :.. * . *: *::* * . .:* .*
gi|29836496|ref|NP_828851.1| MIAAYTAALVSGTATAGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYE 900
gi|30173397|sp|P59594|VGL2_CVH MIAAYTAALVSGTATAGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYE 900
gi|30023954|gb|AAP13567.1| MIAAYTAALVSGTATAGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYE 900
gi|5821923|pdb|1BWM|A YKDDDDKRSGGGGSGGGGSGGSGAQQQVRQSPQSLTVWEGETTILNCSYE 163
.* : .* : *:** *: : * ::* . * **
gi|29836496|ref|NP_828851.1| NQKQIANQFNKAISQIQESLTTTSTALGKLQDVVNQNAQALNTLVKQLSS 950
gi|30173397|sp|P59594|VGL2_CVH NQKQIANQFNKAISQIQESLTTTSTALGKLQDVVNQNAQALNTLVKQLSS 950
gi|30023954|gb|AAP13567.1| NQKQIANQFNKAISQIQESLTTTSTALGKLQDVVNQNAQALNTLVKQLSS 950
gi|5821923|pdb|1BWM|A DSTFDYFPWYR--------------------------------------- 174
:.. : :
gi|29836496|ref|NP_828851.1| NFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEI 1000
gi|30173397|sp|P59594|VGL2_CVH NFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEI 1000
gi|30023954|gb|AAP13567.1| NFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEI 1000
gi|5821923|pdb|1BWM|A QFPGKSPALLIAISLVSNKKEDGRFTIFFNKREKKLSLHITDSQPGDSAT 224
:* . *..* :* :.: : : :: ::. * :.*. ::*:. :
gi|29836496|ref|NP_828851.1| RASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQAAPHGVVFLHVTYV 1050
gi|30173397|sp|P59594|VGL2_CVH RASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQAAPHGVVFLHVTYV 1050
gi|30023954|gb|AAP13567.1| RASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQAAPHGVVFLHVTYV 1050
gi|5821923|pdb|1BWM|A YFCA--ATGSFNKLTFGAGTRLAVS-------------PY---------- 249
.* *: .:.: .:* ..*: .. *:
As can be seen above, there are 45 direct hits in the SARS E2-spike protein/1BWM_A protein multiple sequence alignment; there are 58 closely related hits; there are 44 distant-but-related matches. The gestalt of the multiple sequence alignment (MSA) above is that there is an important relationship between 1BWM_A protein and SARS E2-spike protein. It would appear a reasonable hypothesis that SARS E2-spike protein is composed of amino acids that are, in particularly stretches of the E2-spike protein, very like T-cell receptor alpha-beta V chain amino acids.
Structural picture of 1BWMA with SARS E2-spike protein amino acid "hits" in the multiple sequence alignment highlighted in yellow:

Note that 1BWMA protein is part of the "T-cell Receptor alpha-beta V chain" family of proteins.
The same 1BWMA protein with human coronavirus OC43 and 229E alignments marked in yellow shows this:

Red area is the "conserved area" of 1BWMA and can be used also to orient both pictures.
The probability that SARS E2-spike protein amino acids would match 1BWMA amino acids at the rate observed is p < .01.
The "sameness" between SARS E2-spike protein and 1BWMA (T-cell Receptor alpha-beta V chain) is statistically significant.