T-cell cross-reactivity is essential for effective immune surveillance but has also been implicated as a pathway to autoimmunity. Previous studies have demonstrated that T-cell receptors (TCRs) that focus on a minimal motif within the peptide are able to facilitate a high level of T-cell cross-reactivity. However, the structural database shows that most TCRs exhibit less focused antigen binding involving contact with more peptide residues. To further explore the structural features that allow the clonally expressed TCR to functionally engage with multiple peptide-major histocompatibility complexes (pMHCs), we examined the ILA1 CD8+ T-cell clone that responds to a peptide sequence derived from human telomerase reverse transcriptase. The ILA1 TCR contacted its pMHC with a broad peptide binding footprint encompassing spatially distant peptide residues. Despite the lack of focused TCR-peptide binding, the ILA1 T-cell clone was still cross-reactive. Overall, the TCR-peptide contacts apparent in the structure correlated well with the level of degeneracy at different peptide positions. Thus, the ILA1 TCR was less tolerant of changes at peptide residues that were at, or adjacent to, key contact sites. This study provides new insights into the molecular mechanisms that control T-cell cross-reactivity with important implications for pathogen surveillance, autoimmunity, and transplant rejection.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2jFW2P7
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Introduction. Congenital Palmaris Longus (PL) absence was found in 15%–20.25% of population globally. This condition and Flexor Digitorum Su...
-
Ankylosing spondylitis (AS) is a systemic autoimmune disease mainly affecting the lumbar spine and sacroiliac joints, and exhibits periphera...
-
Differential Effect of Hypoalbuminemia on Hypoglycemia on Type 2 Diabetes Patients Treated with Insulin Glargine 300 U/ml and Insulin Deglud...
-
Abstract An electrochemical DNA biosensor based on a G-quadruplex (G4) for the sensitive determination of Pb 2+ was reported using a carb...
-
A drug first designed to prevent cancer cells from multiplying has a second effect: it switches immune cells that turn down the body's a...
-
HIV Positivity and Referral to Treatment Following Testing of Partners and Children of PLHIV Index Patients in Public Sector Facilities in S...
-
The majority of hematologist-oncologists who use the social media platform Twitter had some financial conflict of interest, according to new...
-
Contact Dermatitis Early View Online Version of Record before inclusion in an issue ORIGINAL ARTICLESAllergic... Contact Dermatitis Early V...
-
Governments of all political persuasions over the past 20 years have made bold promises to reform the way social care is funded. All have di...
-
In the Original Investigation titled “Yield Strength Testing in Human Cadaver Nasal Septal Cartilage and L-Strut Constructs,” published in t...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου