Search PubMed⌕ Search

PubMed · 10938966

MHC: function and implication on vaccine development.

Abstract

The purpose of this State of the Art review is to present an overview of structural and functional aspects of human MHC molecules and how polymorphisms in HLA molecules determine the nature of the antigenic peptides bound and how such may impact upon rational vaccine development. The following areas will be discussed: elements of immune recognition, class I and class II structure and function, the class I antigen processing pathway, class II antigen processing and presentation, functional divergence among T-cells recognizing class I or class II MHC molecules, and rational vaccine development. While the first section will review our current understanding of MHC structure and function, the latter part will draw on my own work with Hepatitis C Virus (HCV) antigens.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

D D Eckels. 2000. MHC: function and implication on vaccine development.. https://pubmed.ncbi.nlm.nih.gov/10938966/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Natural variation of immune epitopes reveals intrabacterial antagonism.

Plants and animals detect biomolecules termed microbe-associated molecular patterns (MAMPs) and induce immunity. Agricultural production is severely impacted by pathogens which can be controlled by transferring immune receptors. However, most studies use a single MAMP epitope and the impact of diverse multicopy MAMPs on immune induction is unknown. Here, we characterized the epitope landscape from five proteinaceous MAMPs across 4,228 plant-associated bacterial genomes. Despite the diversity sampled, natural variation was constrained and experimentally testable. Immune perception in both Arabidopsis and tomato depended on both epitope sequence and copy number variation. For example, Elongation Factor Tu is predominantly single copy, and 92% of its epitopes are immunogenic. Conversely, 99.9% of bacterial genomes contain multiple cold shock proteins, and 46% carry a nonimmunogenic form. We uncovered a mechanism for immune evasion, intrabacterial antagonism, where a nonimmunogenic cold shock protein blocks perception of immunogenic forms encoded in the same genome. These data will lay the foundation for immune receptor deployment and engineering based on natural variation.

Epitopes↗

Determination of the binding specificity of an integral membrane protein by saturation transfer difference NMR: RGD peptide ligands binding to integrin alphaIIbbeta3.

Saturation transfer difference (STD) NMR is a fast and versatile method to screen compound mixtures in the presence of a receptor for binding affinity and to characterize the ligand's binding epitope. Here we demonstrate that ligand interactions with integral membrane proteins can be investigated by STD NMR if the receptor is embedded into the lipid bilayer of a liposome. The integrin alphaIIbbeta3, also termed GPIIb-IIIa, is a platelet surface glycoprotein that plays a pivotal role in platelet aggregation and that interacts with proteins and peptides presenting the peptide recognition motif RGD. Purified human integrin alphaIIbbeta3 was incorporated into liposomes, and the binding of RGD peptides was analyzed by STD NMR techniques. Cyclo(RGDfV) gave STD NMR effects in the presence of liposomes containing the integrin. The magnitude of the STD effect as a function of the ligand's concentration gave a value for the dissociation constant of 30-60 microM. Adding the weakly binding RGD to the solution of cyclo(RGDfV) resulted in STD effects of the stronger ligand cyclo(RGDfV) only. This demonstrates in agreement with literature that the peptide RGD is a much weaker ligand to the integrin than the peptide cyclo(RGDfV) that largely replaces the RGD peptides from the binding site. The binding epitope of the ligand cyclo(RGDfV) was characterized by STD NMR to contain sections of the D-Phe, the Val methyl groups, Arg alpha, beta, and gamma protons, one Hbeta of Asp, and one Halpha of Gly.

Epitopes↗