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

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 -