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

Abstract

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 V_H 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 μM 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.