Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group LRRYLENGK

Under the category of things that make me go "Hm..."

Evelyn got me to thinking (always a dangerous prospect)

And, a caution, eyes-glazing-over-material follows:

Frauendorf E, von Goessel H, May E, Marker-Hermann E. "HLA-B27-restricted T cells from patients with ankylosing spondylitis recognize peptides from B*2705 that are similar to bacteria-derived peptides." Clin Exp Immunol. 2003 Nov;134(2):351-9. PMID: 14616798

Abstract
Ankylosing spondylitis (AS) is an inflammatory systemic disease affecting the spine, sacroiliacal and peripheral joints. Although the aetiology of AS remains unknown, the strong association with the HLA-B27 allele might reflect directly a detrimental effect of the HLA-B27 molecule itself, resulting from its potential capability to present 'arthritogenic' peptides to CD8+ T cells. Because some forms of SpA are triggered by enterobacterial infection, such arthritogenic peptides might originate from autologous and/or bacterial proteins triggering cross-reactive CD8+ T cell clones.

Intriguingly, two peptides from the second extracellular domain of HLA-B*2705 share sequence homologies with several enterobacterial antigens, exhibit the HLA-B27-binding-motif, and are presented by HLA-B*2705 itself.

The objective of this study was to examine the clonal T cell reactivity against these peptides in patients with AS. To this end, we screened peripheral blood lymphocytes (PBL) of 26 patients with AS and 24 healthy donors for TNF-alpha-producing cells using ELISPOT assays. PBL and synovial fluid-derived lymphocytes (SFL) of peptide-responsive patients were then stimulated and cultured with the relevant peptide and control peptides in vitro. Antigen-specific T cell lines (TCL) were identified by standard chromium release assays. Clonal analysis was performed subsequently applying TCRB-CDR3 spectratyping.

Among eight peptides tested, only the HLA-B27 168-176 peptide LRRYLENGK was recognized by PBL from B27+ AS patients but not from B27+ healthy controls (P=0.001). LRRYLENGK-specific T cell clones used preferentially the TCRBV5S1 and the BV14 segment. These results suggest that an HLA-B27-derived peptide with homology to bacterial peptides may play a role in AS. (My emphasis)

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So, that might account for why earlier researchers thought it was bacteria, eh?

Best regards,

just a lowly serf far, far from the ivory towers of biological research



And, apologies for the title... Yeah, I know, it's easier to pronounce if your Welsh.

Very interesting info. And, by the way, you slay me!

it seems to me that there are a couple of questions to ask about the LRRYLENGK sequence explored as a potential AS-associated arthritogenic peptide in the paper Jonathan has cited (Frauendorf et al, Clin Exp Immunol. 2003 134:351-9)

question 1)
peptides homologous to LRRYLENGK originate from which bacteria?

from the text of the Frauendorf paper:
“…One of these nonapeptides that was derived from the 3rd hypervariable region of the HLA-B27 molecule (LRRYLENGK, HLA-B27 168-176) was demonstrated to bind to HLA-B*2705 in vitro[12]. Interestingly, it showed sequence homologies to different bacterial antigens derived from Escherichia coli, Pseudomonas aeruginosa and Bacillus megaterium….”

question 2)
is the LRRYLENGK sequence unique to HLA B27 or is it found in other HLA molecules?

from the text of the same article:
“…It is important to note that this peptide (LRRYLENGK) is not unique to HLA-B27, but also exists in numerous other HLA-A and HLA-B alleles that are not associated with SpA. However, this does not necessarily speak against a role of this peptide in SpA but suggests rather that additional preconditions are to be met to induce the disease. ..”