Presentation of antigenic peptides by products of the major histocompatibility complex

Abstract

Molecules encoded by the major histocompatibility complex (MHC) are polymorphic integral membrane proteins adapted to the presentation of peptide fragments of foreign antigens to antigen-specific T-cells. The diversity of infectious agents to which an immune response must be mounted poses a unique problem for receptor-ligand interactions; how can proteins whose polymorphism is necessarily limited bind an array of peptides almost infinite in its complexity? Both MHC class I and class II determinants have achieved this goal by harnessing a limited number of peptide side chains to anchor the epitope in place while exploiting conserved features of peptide structure, independent of their primary sequence. While class I molecules interact predominantly with the N- and C-termini of peptides, class II determinants form an extensive hydrogen bonding network along the length of the peptide backbone. Such a strategy ensures high-affinity binding, while selectively exposing the unique features of each ligand for recognition by the T-cell receptor.

Molecular Characteristics, Functional Definitions, and Regulatory Mechanisms for Cross-Presentation Mediated by the Major Histocompatibility Complex: A Comprehensive Review

“…MHC I molecules deliver exogenous antigens through two main pathways: the cytosolic pathway (also known as the TAP-dependent pathway) and the vesicular pathway (also known as the TAP-independent pathway) [ 65 ]. Both pathways of antigen presentation involve three essential steps: the degradation of antigens into short peptides [ 66 ], the formation of MHC I short peptide complexes [ 67 ], and the transportation of these complexes to the cell surface [ 68 ].…”