Abstract
Language | English |
---|---|
Article number | 1700253 |
Number of pages | 11 |
Journal | Proteomics |
Volume | 18 |
Issue number | 12 |
DOIs | |
Publication status | Published - Jun 2018 |
Keywords
- HLA-B*57:01
- immunopeptidome
- human immunodeficiency virus
- kynurenine
- posttranslational modification
Cite this
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Identification of native and posttranslationally modified HLA-B*57:01- restricted HIV envelope derived epitopes using immunoproteomics. / Ramarathinam, Sri H.; Gras, Stephanie; Alcantara, Sheilajen; Yeung, Amanda W.S.; Mifsud, Nicole A.; Sonza, Secondo ; Illing, Patricia; Glaros, Elias N; Center, Robert J.; Thomas, Shane R.; Kent, Stephen J.; Ternette, Nicola; Purcell, Damian F J; Rossjohn, Jamie; Purcell, Anthony W.
In: Proteomics, Vol. 18, No. 12, 1700253, 06.2018.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Identification of native and posttranslationally modified HLA-B*57:01- restricted HIV envelope derived epitopes using immunoproteomics
AU - Ramarathinam, Sri H.
AU - Gras, Stephanie
AU - Alcantara, Sheilajen
AU - Yeung, Amanda W.S.
AU - Mifsud, Nicole A.
AU - Sonza, Secondo
AU - Illing, Patricia
AU - Glaros, Elias N
AU - Center, Robert J.
AU - Thomas, Shane R.
AU - Kent, Stephen J.
AU - Ternette, Nicola
AU - Purcell, Damian F J
AU - Rossjohn, Jamie
AU - Purcell, Anthony W.
PY - 2018/6
Y1 - 2018/6
N2 - The recognition of pathogen‐derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the ER. These peptide‐HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T‐cells leading to the eradication of the infected cell. Here, naturally presented HLA‐B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv) are identified. HIVenv peptides are present at a very small percentage of the overall HLA‐B*57:01 peptidome (<0.1%) and both native and posttranslationally modified forms of two distinct HIV peptides are identified. Notably, a peptide bearing a natively encoded C‐terminal tryptophan residue is also present in a modified form containing a kynurenine residue. Kynurenine is a major product of tryptophan catabolism and is abundant during inflammation and infection. Binding of these peptides at a molecular level and their immunogenicity in preliminary functional studies are examined. Modest immune responses are observed to the modified HIVenv peptide, highlighting a potential role for kynurenine‐modified peptides in the immune response to HIV and other viral infections.
AB - The recognition of pathogen‐derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the ER. These peptide‐HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T‐cells leading to the eradication of the infected cell. Here, naturally presented HLA‐B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv) are identified. HIVenv peptides are present at a very small percentage of the overall HLA‐B*57:01 peptidome (<0.1%) and both native and posttranslationally modified forms of two distinct HIV peptides are identified. Notably, a peptide bearing a natively encoded C‐terminal tryptophan residue is also present in a modified form containing a kynurenine residue. Kynurenine is a major product of tryptophan catabolism and is abundant during inflammation and infection. Binding of these peptides at a molecular level and their immunogenicity in preliminary functional studies are examined. Modest immune responses are observed to the modified HIVenv peptide, highlighting a potential role for kynurenine‐modified peptides in the immune response to HIV and other viral infections.
KW - HLA-B57:01
KW - immunopeptidome
KW - human immunodeficiency virus
KW - kynurenine
KW - posttranslational modification
U2 - 10.1002/pmic.201700253
DO - 10.1002/pmic.201700253
M3 - Article
VL - 18
JO - Proteomics
T2 - Proteomics
JF - Proteomics
SN - 1615-9853
IS - 12
M1 - 1700253
ER -