Peptide binding and antigen presentation by class II histocompatibility glycoproteins

Jensen, Peter E.

doi:10.1002/(sici)1097-0282(1997)43:4<303::aid-bip4>3.0.co;2-z

Cited by 10 publications

(2 citation statements)

References 163 publications

(14 reference statements)

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“…Highly stable pMHCII complexes have been shown to be relatively resistant to DM activity, as evidenced by the marginal enhancement of peptide dissociation rates, which has led to the proposal of a linear relationship between the observed peptide dissociation rate and DM concentration (6,9,28,45,47). We evaluated peptide dissociation rates with increasing concentrations of DM and consistently observed upper rate limits with higher concentrations of HLA-DM ( Fig.…”

Section: Hla-dm-catalyzed Peptide Dissociation Rates Are Saturable Ementioning

confidence: 87%

HLA-DM catalytically enhances peptide dissociation by sensing peptide–MHC class II interactions throughout the peptide-binding cleft

Reyes-Vargas

Barker

Zhou

et al. 2020

Journal of Biological Chemistry

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Human leukocyte antigen-DM (HLA-DM) is an integral component of the major histocompatibility complex class II (MHCII) antigen-processing and -presentation pathway. HLA-DM shapes the immune system by differentially catalyzing peptide exchange on MHCII molecules, thereby editing the peptide-MHCII (pMHCII) repertoire by imposing a bias on the foreign and self-derived peptide cargos that are presented on the cell surface for immune surveillance and tolerance induction by CD4+ T cells. To better understand DM selectivity, here we developed a real-time fluorescence anisotropy assay to delineate the pMHCII intrinsic stability, DM-binding affinity, and catalytic turnover, independent kinetic parameters of HLA-DM enzymatic activity. We analyzed prominent pMHCII contacts by differentiating the kinetic parameters in pMHCII homologs, observing that peptide interactions throughout the MHCII-binding cleft influence both the rate of peptide dissociation from the DM-pMHCII catalytic complex and the binding affinity of HLA-DM for a pMHCII. We show that the intrinsic stability of a pMHCII linearly correlates with DM catalytic turnover, but is nonlinearly correlated with its binding affinity. Surprisingly, interactions at the peptides N terminus up to and including MHCII position one (P1) anchor affected the catalytic turnover, suggesting that the active DM-pMHCII catalytic complex operates on pMHCII complexes with full peptide occupancy. Furthermore, interactions at the peptide C terminus modulated DM-binding affinity, suggesting distal communication between peptide interactions with the MHCII and the DM-pMHCII binding interface. Our results imply an intimate linkage between the DM-pMHCII interface and peptide-MHCII interactions throughout the peptide-binding cleft.

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Section: Hla-dm-catalyzed Peptide Dissociation Rates Are Saturable Ementioning

confidence: 87%

HLA-DM catalytically enhances peptide dissociation by sensing peptide–MHC class II interactions throughout the peptide-binding cleft

Reyes-Vargas

Barker

Zhou

et al. 2020

Journal of Biological Chemistry

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“…Two distinct intracellular pathways have evolved to generate class I and class II MHC-peptide complexes (4,5). Two distinct intracellular pathways have evolved to generate class I and class II MHC-peptide complexes (4,5).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Antigen Presentation

Jensen¹

1999

CCLM

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T-lymphocytes recognize short peptide antigens bound stably to polymorphic major histocompatibility complex (MHC)-encoded glycoproteins expressed on the surface of antigen-presenting cells (APC). Two general pathways have evolved to generate peptide-MHC complexes. The MHC class II antigen processing pathway provides a mechanism for sampling proteins present in endosomal compartments. CD4+ regulatory T-cells recognize peptides bound to MHC class II molecules, which are selectively expressed in specialized APC that have efficient mechanisms for uptake of microbial antigens, and express costimulatory molecules required for activating naive T-cells. CD8+ T-cells recognize peptides bound to MHC class I molecules. Class I molecules are widely expressed and bind peptides derived from the normal turnover of cellular proteins, providing a mechanism to display a sampling of cellular components to be monitored for abnormalities by cytotoxic T-cells. Specialized accessory proteins influence the efficiency of antigen presentation and the specificity of immune responses through their roles in generating peptides, targeting antigen and MHC glycoproteins to selected intracellular compartments, and by direct participation in the peptide-loading mechanism. It has recently been discovered that some viruses have evolved ways to inhibit or subvert discrete steps in antigen processing, providing a mechanism to evade immune recognition.

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Mechanisms of Adverse Drug Reactions

Pirmohamed¹

2014

Mann's Pharmacovigilance

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Peptide binding and antigen presentation by class II histocompatibility glycoproteins

Cited by 10 publications

References 163 publications

HLA-DM catalytically enhances peptide dissociation by sensing peptide–MHC class II interactions throughout the peptide-binding cleft

HLA-DM catalytically enhances peptide dissociation by sensing peptide–MHC class II interactions throughout the peptide-binding cleft

Mechanisms of Antigen Presentation

Mechanisms of Adverse Drug Reactions

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