Abstract
Cross-presentation of endocytosed antigen as peptide/class I major histocompatibility complex complexes plays a central role in the elicitation of CD8+ T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells capable of antigen cross-presentation, identification of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC), there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlights DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, maturation-induced endosomal sorting of membrane proteins, dynamic remodeling of endosomal structures and cell surface-directed endosomal trafficking. We will conclude with the description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.
Highlights
Major histocompatibility complex (MHC) restriction of T lymphocytes was first reported by Doherty and Zinkernagel (1975).They provided experimental proof that T cells can only respond to peptide antigens when they are presented in complex with host-derived MHC molecules, existing in a class I and class II variant
CONCLUDING REMARKS Efficient cross-presentation of CD8+ T cells that initiates balanced anti-viral and anti-tumor immune responses depends on dendritic cells (DC)-intrinsic mechanisms that enable the sequential interaction of specific TCR molecules with peptide/MHC complexes in the context of activating or inhibiting signals
The molecular mechanisms described in this review all aid to ensure the quantity and quality of this DC-derived signal toward the CD8+ T cells
Summary
Major histocompatibility complex (MHC) restriction of T lymphocytes was first reported by Doherty and Zinkernagel (1975). They provided experimental proof that T cells can only respond to peptide antigens when they are presented in complex with host-derived MHC molecules, existing in a class I and class II variant. MHC and exogenous antigen on class II MHC is not absolute. He demonstrated that minor histocompatibility antigens from transplanted cells (e.g., exogenous antigen) could prime cytotoxic CD8+ T cells in a host class I MHC-restricted manner and named this process cross-priming. The capability to present exogenous antigens via class
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