8223850

pubmed:Citation

11

Major histocompatibility complex (MHC) class I and II products are specialized to present antigens via different intracellular processing routes. Peptides originating from proteins in the cytoplasm can gain access to class I peptide-binding grooves, most likely in the rough endoplasmic reticulum. Peptides from proteins in acidic endocytic vacuoles gain access to class II. It has been proposed that MHC class I products also can capture peptides from "exogenous" or noninfectious sources, and this assumption underlies the use of intact proteins as vaccines for CD8+ cytotoxic T lymphocytes. Here we describe quantitative information comparing the efficacy of peptide presentation from exogenous proteins by administering a class I- and II-restricted peptide within the same context, the CDR3 loop of the VH domain of a self immunoglobulin. Antigen-presenting cells (APC), including primary dendritic cells, efficiently present an influenza hemagglutinin peptide from the immunoglobulin (Ig) carrier (50% maximal response at 10 nM Ig-HA) to an MHC class II-restricted T cell. In contrast, these same APC are unable to present an influenza nucleoprotein (NP) peptide from the same context (1 microM Ig-NP) to an MHC class I-restricted T cell. Ig-NP DNA transfectants do present the nucleoprotein viral peptide on class I. Thus, peptides within the complementarity-determining region loops of Ig carriers can be presented on class I or II MHC products, but the endocytic compartment, when offered MHC class I- and II-restricted peptides within the same carrier protein context, favors presentation by class II by at least 1000-fold.

eng

IM

MEDLINE

0014-2980

Print

NLM

2746-50

pubmed-meshheading:8223850-Amino Acid Sequence, pubmed-meshheading:8223850-Animals, pubmed-meshheading:8223850-Antigen-Presenting Cells, pubmed-meshheading:8223850-Antigens, pubmed-meshheading:8223850-Cell Line, pubmed-meshheading:8223850-Hemagglutinin Glycoproteins, Influenza Virus, pubmed-meshheading:8223850-Hemagglutinins, Viral, pubmed-meshheading:8223850-Histocompatibility Antigens Class I, pubmed-meshheading:8223850-Histocompatibility Antigens Class II, pubmed-meshheading:8223850-Immunoglobulins, pubmed-meshheading:8223850-Influenza A virus, pubmed-meshheading:8223850-Lymphocyte Activation, pubmed-meshheading:8223850-Mice, pubmed-meshheading:8223850-Mice, Inbred BALB C, pubmed-meshheading:8223850-Molecular Sequence Data, pubmed-meshheading:8223850-Nucleoproteins, pubmed-meshheading:8223850-Peptides, pubmed-meshheading:8223850-RNA-Binding Proteins, pubmed-meshheading:8223850-T-Lymphocyte Subsets, pubmed-meshheading:8223850-Viral Core Proteins

Contrasting efficacy of presentation by major histocompatibility complex class I and class II products when peptides are administered within a common protein carrier, self immunoglobulin.

Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't