MHC Class I–Restricted CTL Responses to Exogenous Antigens

• Published in: Immunity 1996-10, Vol.5 (4), p.295-302
• Main Authors: Jondal, Mikael, Schirmbeck, Reinhold, Reimann, Jörg
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigens - metabolism; Cytotoxicity, Immunologic; Histocompatibility Antigens Class I - physiology; Humans; Immunity, Cellular; Peptides - immunology; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80255-1

Different processing pathways operate for major histocompatibility complex (MHC)-restricted peptide presentation of exogenous and endogenous antigens. Exogenous antigens are internalized by antigen-presenting cells (APC) and degraded at an acid pH in vesicular intracellular compartments. Generated peptides are then loaded onto MHC class II (MHC-II) molecules and presented at the cell surface to CD4 super(+) helper T cells. In the cytoplasm, peptides are generated from endogenous antigens by degradation involving a multicatalytic proteinase complex, the proteasome. Cytosolic peptides are transported into the endoplasmic reticulum (ER) lumen by ATP-dependent transporters associated with antigen presentation (TAPs). In the ER lumen, peptides bind to nascent MHC class I (MHC-I) molecules in a chaperone-assisted assembly that generates stable trimeric MHC-I heavy chain- beta sub(2)-microglobulin-peptide complexes. These transport- and presentation-competent complexes move to the cell surface for recognition and activation of CD8 super(+) cytotoxic T lymphocytes (CTL). This clear-cut dichotomy between an exogenous processing pathway for MHC-II-restricted T cell response and an endogenous pathway for MHC-I-restricted T cell response is supported by extensive experimental data. However, recent data show that the injection of various types of exogenous antigens efficiently prime MHC-I-restricted CTL responses. Here, we briefly summarize these findings and discuss potential uptake mechanisms and processing pathways for exogenous antigens. Although little is yet known about alternative MHC-I processing pathways in APC, evidence for phagocytic and nonphagocytic processing pathways is emerging.