Identification of native and posttranslationally modified HLA-B*57:01- restricted HIV envelope derived epitopes using immunoproteomics

Sri H. Ramarathinam, Stephanie Gras, Sheilajen Alcantara, Amanda W.S. Yeung, Nicole A. Mifsud, Secondo Sonza, Patricia Illing, Elias N Glaros, Robert J. Center, Shane R. Thomas, Stephen J. Kent, Nicola Ternette, Damian F J Purcell, Jamie Rossjohn, Anthony W. Purcell

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
LanguageEnglish
Article number1700253
Number of pages11
JournalProteomics
Volume18
Issue number12
DOIs
Publication statusPublished - Jun 2018

Keywords

  • HLA-B*57:01
  • immunopeptidome
  • human immunodeficiency virus
  • kynurenine
  • posttranslational modification

Cite this

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. / Identification of native and posttranslationally modified HLA-B*57:01- restricted HIV envelope derived epitopes using immunoproteomics. In: Proteomics. 2018 ; Vol. 18, No. 12.
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abstract = "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.",
keywords = "HLA-B*57:01, immunopeptidome, human immunodeficiency virus, kynurenine, posttranslational modification",
author = "Ramarathinam, {Sri H.} and Stephanie Gras and Sheilajen Alcantara and Yeung, {Amanda W.S.} and Mifsud, {Nicole A.} and Secondo Sonza and Patricia Illing and Glaros, {Elias N} and Center, {Robert J.} and Thomas, {Shane R.} and Kent, {Stephen J.} and Nicola Ternette and Purcell, {Damian F J} and Jamie Rossjohn and Purcell, {Anthony W.}",
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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 journalArticleResearchpeer-review

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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.

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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

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M1 - 1700253

ER -